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BIOLOGY (1342 journals)            First | 6 7 8 9 10 11 12 13 | Last

Mammalian Genome     Hybrid Journal   (Followers: 3)
Mammalian Species     Full-text available via subscription   (Followers: 2)
Manufacturing Engineer     Hybrid Journal   (Followers: 3)
Marine Biodiversity     Hybrid Journal   (Followers: 10)
Marine Biodiversity Records     Hybrid Journal   (Followers: 7)
Marine Biology     Hybrid Journal   (Followers: 194)
Marine Biotechnology     Hybrid Journal   (Followers: 6)
Marine Mammal Science     Hybrid Journal   (Followers: 6)
Materials Science and Engineering: C     Hybrid Journal   (Followers: 16)
Mathematical Biosciences     Hybrid Journal   (Followers: 3)
Mathematical Medicine and Biology: A Journal of the IMA     Hybrid Journal   (Followers: 2)
Mathematical Physics, Analysis and Geometry     Hybrid Journal   (Followers: 1)
Mathematical Problems in Engineering     Open Access   (Followers: 3)
Matrix Biology     Hybrid Journal  
Médecine Nucléaire     Full-text available via subscription  
mBio     Open Access   (Followers: 3)
Mechanisms of Ageing and Development     Hybrid Journal   (Followers: 2)
Mechanisms of Development     Hybrid Journal   (Followers: 4)
médecine/sciences     Full-text available via subscription   (Followers: 1)
Medical and Biological Engineering and Computing     Hybrid Journal   (Followers: 2)
Medical and Biological Sciences     Open Access  
Medical Engineering & Physics     Hybrid Journal   (Followers: 9)
Membrane Protein Transport     Full-text available via subscription   (Followers: 3)
Memoirs of the Association of Australasian Palaeontologists     Full-text available via subscription   (Followers: 2)
Metabolic Engineering     Hybrid Journal   (Followers: 8)
Metabolites     Open Access   (Followers: 1)
Metabolomics     Hybrid Journal   (Followers: 5)
Metallomics     Full-text available via subscription  
Methods     Hybrid Journal   (Followers: 11)
Methods in Cell Biology     Full-text available via subscription   (Followers: 6)
Methods in Cell Science     Hybrid Journal   (Followers: 3)
Methods in Ecology and Evolution     Partially Free   (Followers: 16)
Micologia Aplicada Internacional     Open Access  
Microarrays     Open Access  
Micron     Hybrid Journal  
Mitochondrial DNA     Hybrid Journal   (Followers: 3)
Mitochondrion     Hybrid Journal   (Followers: 3)
Modelling and Simulation in Engineering     Open Access   (Followers: 4)
Modern Chemotherapy     Open Access  
Molecular & Cellular Proteomics     Full-text available via subscription   (Followers: 10)
Molecular & Cellular Toxicology     Hybrid Journal   (Followers: 2)
Molecular and Biochemical Parasitology     Hybrid Journal   (Followers: 2)
Molecular and Cellular Biochemistry     Hybrid Journal   (Followers: 4)
Molecular and Cellular Biology     Full-text available via subscription   (Followers: 19)
Molecular Based Mathematical Biology     Open Access  
Molecular Biology     Hybrid Journal   (Followers: 10)
Molecular Biology and Evolution     Hybrid Journal   (Followers: 212)
Molecular Biology International     Open Access   (Followers: 3)
Molecular Biology of the Cell     Partially Free   (Followers: 16)
Molecular Biology Reports     Hybrid Journal   (Followers: 4)
Molecular Brain     Open Access   (Followers: 2)
Molecular Breeding     Hybrid Journal   (Followers: 6)
Molecular Cell     Full-text available via subscription   (Followers: 38)
Molecular Ecology     Hybrid Journal   (Followers: 22)
Molecular Ecology Resources     Hybrid Journal   (Followers: 10)
Molecular Genetics and Metabolism     Hybrid Journal   (Followers: 5)
Molecular Immunology     Hybrid Journal   (Followers: 12)
Molecular Membrane Biology     Hybrid Journal   (Followers: 1)
Molecular Neurobiology     Hybrid Journal   (Followers: 3)
Molecular Pain     Open Access  
Molecular Plant-Microbe Interactions     Partially Free   (Followers: 5)
Molecular Reproduction & Development     Hybrid Journal   (Followers: 7)
Molecular Therapy - Nucleic Acids     Open Access  
Molecules and Cells     Hybrid Journal   (Followers: 1)
Momona Ethiopian Journal of Science     Open Access   (Followers: 2)
Monoclonal Antibodies in Immunodiagnosis and Immunotherapy     Hybrid Journal  
Monographs of the Western North American Naturalist     Full-text available via subscription   (Followers: 1)
Moscow University Physics Bulletin     Hybrid Journal  
Movement Ecology     Open Access   (Followers: 4)
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis     Hybrid Journal   (Followers: 2)
Mutation Research/Genetic Toxicology and Environmental Mutagenesis     Hybrid Journal   (Followers: 7)
Mutation Research/Reviews in Mutation Research     Hybrid Journal   (Followers: 4)
Mycological Progress     Hybrid Journal   (Followers: 1)
Mycopathologia     Hybrid Journal   (Followers: 1)
Mycorrhiza     Hybrid Journal   (Followers: 5)
Mycoscience     Hybrid Journal   (Followers: 1)
Mycotoxin Research     Hybrid Journal   (Followers: 4)
NAMMCO Scientific Publications     Open Access  
Nano Reviews     Open Access   (Followers: 17)
Nano Today     Hybrid Journal   (Followers: 15)
Nanoscale Research Letters     Open Access   (Followers: 4)
Natural Hazards     Hybrid Journal   (Followers: 283)
Natural History     Full-text available via subscription   (Followers: 4)
Natural Product Research: Formerly Natural Product Letters     Hybrid Journal   (Followers: 1)
Natural Science     Open Access   (Followers: 9)
Nature     Full-text available via subscription   (Followers: 2576)
Nature Cell Biology     Full-text available via subscription   (Followers: 308)
Nature China     Full-text available via subscription   (Followers: 6)
Nature Digest     Full-text available via subscription   (Followers: 5)
Nature Protocols     Full-text available via subscription   (Followers: 40)
Nature Reviews Molecular Cell Biology     Full-text available via subscription   (Followers: 263)
Nature Structural & Molecular Biology     Full-text available via subscription   (Followers: 226)
Naturwissenschaften     Hybrid Journal   (Followers: 4)
Nauplius     Open Access  
Nematology     Hybrid Journal   (Followers: 2)
Nematropica     Open Access  
NeoBiota     Open Access   (Followers: 2)
Neotropical Ichthyology     Open Access  
Nepal Journal of Science and Technology     Open Access  
Neurobiology of Aging     Hybrid Journal   (Followers: 4)

  First | 6 7 8 9 10 11 12 13 | Last

Journal Cover Biochemistry and Cell Biology     [SJR: 1.488]   [H-I: 65]
   [10 followers]  Follow    
   Full-text available via subscription Subscription journal
   ISSN (Print) 0829-8211 - ISSN (Online) 1208-6002
   Published by NRC Research Press Homepage  [18 journals]
  • MicroRNA regulatory networks in idiopathic pulmonary fibrosis
    • Authors: Kusum V. Pandit, Jadranka Milosevic
      Pages: 1 - 9
      Abstract: Biochemistry and Cell Biology, e-First Articles. Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal scarring lung disease of unknown etiology, characterized by changes in microRNA expression. Activation of transforming growth factor (TGF-β) is a key event in the development of IPF. Recent reports have also identified epigenetic modification as an important player in the pathogenesis of IPF. In this review, we summarize the main results of studies that address the role of microRNAs in IPF and highlight the synergistic actions of these microRNAs in regulating TGF-β, the primary fibrogenic mediator. We outline epigenetic regulation of microRNAs by methylation. Functional studies identify microRNAs that alter proliferative and migratory properties of fibroblasts, and induce phenotypic changes in epithelial cells consistent with epithelial-mesenchymal transition. Though these studies were performed in isolation, we identify multiple co-operative actions after assembling the results into a network. Construction of such networks will help identify disease-propelling hubs that can be targeted for therapeutic purposes.
      Citation: Biochemistry and Cell Biology
      PubDate: Mon, 05 Jan 2015 12:51:20 GMT
      DOI: 10.1139/bcb-2014-0101
  • Biochemistry and Cell Biology
    • Pages: 1 - 30
      Abstract: Biochemistry and Cell Biology, e-First Articles.
      PubDate: Fri, 19 Sep 2014 11:47:19 GMT
      DOI: 10.1139/bcb-2014-0111
      Issue No: Vol. 0, No. 0 (2014)
  • The apelin receptor: physiology, pathology, cell signalling, and ligand
           modulation of a peptide-activated class A GPCR
    • Authors: Nigel A. Chapman, Denis J. Dupré, Jan K. Rainey
      Pages: 1 - 10
      Abstract: Biochemistry and Cell Biology, e-First Articles. The apelin receptor (AR or APJ) is a class A (rhodopsin-like) G-protein-coupled receptor with wide distribution throughout the human body. Activation of the AR by its cognate peptide ligand, apelin, induces diverse physiological effects including vasoconstriction and dilation, strengthening of heart muscle contractility, angiogenesis, and regulation of energy metabolism and fluid homeostasis. Recently, another endogenous peptidic activator of the AR, Toddler/ELABELA, was identified as having a crucial role in zebrafish (Danio rerio) embryonic development. The AR is also implicated in pathologies including cardiovascular disease, diabetes, obesity, and cancer, making it a promising therapeutic target. Despite its established importance, the precise roles of AR signalling remain poorly understood. Moreover, little is known about the mechanisms of peptide–AR activation. Additional complexity arises from modulation of the AR by 2 endogenous peptide ligands, both with multiple bioactive isoforms of variable length and distribution. The various apelin and Toddler/ELABELA isoforms may also produce distinct cellular effects. Further complexity arises through formation of functionally distinct heterodimers between the AR and other G-protein-coupled receptors. This minireview outlines key (patho)physiological actions of the AR, addresses what is known about signal transduction downstream of AR activation, and concludes by discussing unique properties of the endogenous peptidic ligands of the AR.
      Citation: Biochemistry and Cell Biology
      PubDate: Wed, 20 Aug 2014 07:00:00 GMT
      DOI: 10.1139/bcb-2014-0072
      Issue No: Vol. 0, No. 0 (2014)
  • Functional interdependence of NHE1 and merlin in human melanoma cells
    • Authors: Fabian Frontzek, Svenja Nitzlaff, Malte Horstmann, Albrecht Schwab, Christian Stock
      Pages: 1 - 11
      Abstract: Biochemistry and Cell Biology, e-First Articles. Upregulation of the Na+/H+ exchanger isoform 1 (NHE1) has been correlated with tumor malignancy. In contrast, moesin-radixin-ezrin–like protein (merlin) is a tumor suppressor that protects from cancerogenesis. Merlin is highly related to the members of the ezrin, radixin, and moesin (ERM) protein family that are directly attached to and functionally linked with NHE1. In addition, merlin inhibits the MAPK cascade and the Rho-GTPases known to activate NHE1 activity. The present study investigates whether NHE1 expression and activity affect merlin or, conversely, whether merlin has an impact on NHE1 in human melanoma (MV3) cells. Indeed, features of merlin-deficient MV3 cells point to a functional link: merlin-deficient cells showed a decreased NHE1 expression and, paradoxically, an increase in NHE1 activity as measured upon cytosolic acidification (NH4Cl prepulse method). Loss of merlin also led to an elevated cell motility that could be further increased by NHE1 overexpression, whereas NHE1 overexpression alone had no effect on migration. In contrast, neither NHE1 expression nor its activity had an impact on merlin expression. These results suggest a novel tumor suppressor function of merlin in melanoma cells: the inhibition of the proto-oncogenic NHE1 activity, possibly including its downstream signaling pathways.
      Citation: Biochemistry and Cell Biology
      PubDate: Wed, 06 Aug 2014 07:00:00 GMT
      DOI: 10.1139/bcb-2014-0041
      Issue No: Vol. 0, No. 0 (2014)
  • Characterization of human mutations in phosphorylatable amino acids of the
           cytosolic regulatory tail of SLC9A1
    • Authors: Claudia Alves, Yike Ma, Xiuju Li, Larry Fliegel
      Pages: 1 - 6
      Abstract: Biochemistry and Cell Biology, e-First Articles. The NHE1 isoform of the mammalian Na+/H+ exchanger is a ubiquitous plasma membrane protein that regulates intracellular pH in cells by removing one intracellular proton in exchange for one extracellular sodium. Genetic defects in NHE1 have been shown to affect the growth and motor ability of mice, but mutations in humans have not been studied. NHE1 has a cytosolic C-terminal regulatory domain of approximately 300 amino acids. We investigated the functional effects of two human mutations found in the regulatory phosphorylatable amino acids Ser703 and Ser771. A Ser703Pro mutant protein had essentially the same activity, expression, and targeting as the wild type NHE1 protein. In contrast, the Ser771Pro protein had reduced activity and expression of NHE1 protein, though cell surface targeting was normal. In dual pulse assays the Ser771Pro mutant was not further activated by sustained intracellular acidosis but displayed an unusual activation by brief pulses of acidosis. The results demonstrate that the Ser771Pro human genetic mutation has significant and detrimental physiological effects on the activity of the NHE1 protein, SLC9A1.
      Citation: Biochemistry and Cell Biology
      PubDate: Wed, 23 Jul 2014 07:00:00 GMT
      DOI: 10.1139/bcb-2014-0071
      Issue No: Vol. 0, No. 0 (2014)
  • Lessons from a red squirrel, mentors, and the pathway to success
    • Authors: Reinhart A.F. Reithmeier
      Pages: 1 - 4
      Abstract: Biochemistry and Cell Biology, e-First Articles. In this article I will review my personal career path starting with how a red squirrel got me interested in research, and the vital role that mentors played in my pathway to success — a pathway that taught me many lessons that I would like to share with the reader, particularly graduate students and post-doctoral fellows who are just starting down their own unique pathways.
      Citation: Biochemistry and Cell Biology
      PubDate: Mon, 23 Jun 2014 07:00:00 GMT
      DOI: 10.1139/bcb-2014-0058
      Issue No: Vol. 0, No. 0 (2014)
  • Protein transport into the human ER and related diseases,
    • Authors: Sarah Haßdenteufel, Marie-Christine Klein, Armin Melnyk, Richard Zimmermann
      Pages: 1 - 11
      Abstract: Biochemistry and Cell Biology, e-First Articles. Protein transport into the human endoplasmic reticulum (ER) is relevant to the biogenesis of most soluble and membrane proteins of organelles, which are involved in endo- or exo-cytsosis. It involves amino-terminal signal peptides in the precursor polypeptides and various transport components in the cytosol plus the ER, and can occur co- or post-translationally. The two mechanisms merge at the level of the ER membrane, specifically at the level of the heterotrimeric Sec61 complex, which forms a dynamic polypeptide-conducting channel in the ER membrane. Since the mammalian ER is also the main intracellular calcium storage organelle, and the Sec61 complex is calcium permeable, the Sec61 complex is tightly regulated in its equilibrium between the closed and open conformations, or “gated”, by ligands, such as signal peptides of the transport substrates and the ER lumenal Hsp70-type molecular chaperone BiP. Furthermore, BiP binding to the incoming polypeptide contributes to the efficiency and unidirectionality of transport. Recent insights into the structure and dynamic equilibrium of the Sec61 complex have various mechanistic as well as medical implications.
      Citation: Biochemistry and Cell Biology
      PubDate: Tue, 27 May 2014 07:00:00 GMT
      DOI: 10.1139/bcb-2014-0043
      Issue No: Vol. 0, No. 0 (2014)
  • Import of ribosomal proteins into yeast mitochondria
    • Authors: Michael W. Woellhaf, Katja G. Hansen, Christoph Garth, Johannes M. Herrmann
      Pages: 1 - 10
      Abstract: Biochemistry and Cell Biology, e-First Articles. Mitochondrial ribosomes of baker’s yeast contain at least 78 protein subunits. All but one of these proteins are nuclear-encoded, synthesized on cytosolic ribosomes, and imported into the matrix for biogenesis. The import of matrix proteins typically relies on N-terminal mitochondrial targeting sequences that form positively charged amphipathic helices. Interestingly, the N-terminal regions of many ribosomal proteins do not closely match the characteristics of matrix targeting sequences, suggesting that the import processes of these proteins might deviate to some extent from the general import route. So far, the biogenesis of only two ribosomal proteins, Mrpl32 and Mrp10, was studied experimentally and indeed showed surprising differences to the import of other preproteins. In this review article we summarize the current knowledge on the transport of proteins into the mitochondrial matrix, and thereby specifically focus on proteins of the mitochondrial ribosome.
      Citation: Biochemistry and Cell Biology
      PubDate: Tue, 20 May 2014 07:00:00 GMT
      DOI: 10.1139/bcb-2014-0029
      Issue No: Vol. 0, No. 0 (2014)
  • Purification and photobiochemical profile of photosystem 1 from a
           high-salt tolerant, oleaginous Chlorella (Trebouxiophycaea, Chlorophyta)
    • Authors: Michael D. McConnell, David Lowry, Troy N. Rowan, Karin van Dijk, Kevin E. Redding
      Pages: 1 - 11
      Abstract: Biochemistry and Cell Biology, e-First Articles. The eukaryotic green alga Chlamydomonas reinhardtii has been studied extensively within the biofuel industry as a model organism, as researchers look towards algae to provide chemical feedstocks (i.e., lipids) for the production of liquid transportation fuels. C. reinhardtii, however, is unsuitable for high-level production of such precursors due to its relatively poor lipid accumulation and fresh-water demand. In this study we offer insight into the primary light harvesting and electron transfer reactions that occur during phototropic growth in a high-salt tolerant strain of Chlorella (a novel strain introduced here as NE1401), a single-celled eukaryotic algae also in the phylum Chlorophyta. Under nutrient starvation many eukaryotic algae increase dramatically the amount of lipids stored in lipid bodies within their cell interiors. Microscopy and lipid analyses indicate that Chlorella sp. NE1401 may become a superior candidate for algal biofuels production. We have purified highly active Photosystem 1 (PS1) complexes to study in vitro, so that we may understand further the photobiochemisty of this promising biofuel producer and how its characteristics compare and contrast with that of the better understood C. reinhardtii. Our findings suggest that the PS1 complex from Chlorella sp. NE1401 demonstrates similar characteristics to that of C. reinhardtii with respect to light-harvesting and electron transfer reactions. We also illustrate that the relative extent of the light state transition performed by Chlorella sp. NE1401 is smaller compared to C. reinhardtii, although they are triggered by the same dynamic light stresses.
      Citation: Biochemistry and Cell Biology
      PubDate: Tue, 02 Dec 2014 08:00:00 GMT
      DOI: 10.1139/bcb-2014-0144
  • Deception in simplicity: Hereditary phospholamban mutations in dilated
    • Authors: Howard S. Young, Delaine K. Ceholski, Catharine A. Trieber
      Pages: 1 - 7
      Abstract: Biochemistry and Cell Biology, e-First Articles. The sarcoplasmic reticulum (SR) calcium pump (SERCA) and its regulator phospholamban are required for cardiovascular function. Phospholamban alters the apparent calcium affinity of SERCA in a process that is modulated by phosphorylation via the β-adrenergic pathway. This regulatory axis allows for the dynamic control of SR calcium stores and cardiac contractility. Herein we focus on hereditary mutants of phospholamban that are associated with heart failure, such as Arg9-Cys, Arg9-Leu, Arg9-His, and Arg14-deletion. Each mutant has a distinct effect on PLN function and SR calcium homeostasis. Arg9-Cys and Arg9-Leu do not inhibit SERCA, Arg14-deletion is a partial inhibitor, and Arg9-His is comparable to wild-type. While the mutants have distinct functional effects on SERCA, they have in common that they cannot be phosphorylated by protein kinase A (PKA). Arg9 and Arg14 are required for PKA recognition and phosphorylation of PLN. Thus, mutations at these positions eliminate β-adrenergic control and dynamic cardiac contractility. Hydrophobic mutations of Arg9 cause more complex changes in function, including loss of PLN function and dominant negative interaction with SERCA in heterozygous individuals. In addition, aberrant interaction with PKA may prevent phosphorylation of wild-type PLN and sequester PKA from other local subcellular targets. Herein we consider what is known about each mutant and how the synergistic changes in SR calcium homeostasis lead to impaired cardiac contractility and dilated cardiomyopathy.
      Citation: Biochemistry and Cell Biology
      PubDate: Mon, 01 Dec 2014 22:38:40 GMT
      DOI: 10.1139/bcb-2014-0080
  • Berberine as a therapy for type 2 diabetes and its complications: From
           mechanism of action to clinical studies
    • Authors: Wenguang Chang, Li Chen, Grant M. Hatch
      Pages: 1 - 8
      Abstract: Biochemistry and Cell Biology, e-First Articles. The incidence of type 2 diabetes is increasing rapidly worldwide, and the development of novel anti-diabetic drugs is emerging. However, most anti-diabetic drugs cannot be used in patients with hepatic dysfunction, renal disease, and heart disease, which makes pharmacological therapy of type 2 diabetes complicated. Despite continued introduction of novel agents, the search for an ideal drug that is useful as both a hypoglycemic agent and to reduce diabetes-related complications remains elusive. Berberine is an isoquinoline alkaloid extract that has shown promise as a hypoglycemic agent in the management of diabetes in animal and human studies. Mechanistic studies have revealed beneficial effects of berberine on diabetes-related complications. Although there have been few clinical reports of the anti-diabetic effects of berberine, little documentation of adverse effects in humans positions it as a potential candidate drug to treat type 2 diabetes. In the present review, the anti-diabetic mechanism of berberine, its effect on diabetes-related complications, and its recent use in human clinical studies is highlighted. In addition, we summarize the different treatments for type 2 diabetes in adults and children.
      Citation: Biochemistry and Cell Biology
      PubDate: Mon, 01 Dec 2014 08:00:00 GMT
      DOI: 10.1139/bcb-2014-0107
  • Trigonella foenum-graecum ameliorates acrylamide-induced toxicity in rats:
           Roles of oxidative stress, proinflammatory cytokines, and DNA damage
    • Authors: Mohamed M. Abdel-Daim, Mabrouk A. Abd Eldaim, Abeer G.A. Hassan
      Pages: 1 - 7
      Abstract: Biochemistry and Cell Biology, e-First Articles. Acrylamide is a hazardous substance inducing oxidative stress. Based on some evidence on the antioxidant properties of fenugreek, Trigonella foenum-graecum, this study was conducted to investigate the protective effect of fenugreek seed oil against acrylamide toxicity. Thirty-two male Wistar rats were randomly assigned into four groups. The control group was given normal saline. The second group was administered acrylamide (20 mg/kg bw orally). The third and fourth groups were administered acrylamide (20 mg/kg bw) and supplemented with 2.5% and 5% fenugreek seed oil in their diets, respectively. Acrylamide intoxication significantly increased serum levels of LDH, AST, ALT, APL, γ-GT, cholesterol, uric acid, urea, creatinine, 8-oxo-2′-deoxyguanosine, interleukin 1 beta, interleukin 6, and tumor necrosis factor α. Moreover, it increased hepatic, renal, and brain lipid peroxidation, while it impaired the activities and concentrations of the antioxidant biomarkers. Fenugreek oil supplementation normalized the altered serum parameters, prevented lipid peroxidation, and enhanced the antioxidant biomarker concentrations and activities in the hepatic, renal, and brain tissues of acrylamide-intoxicated rats in a dose-dependent manner. Thus, these results indicate that Trigonella foenum-graecum oil has a protective effect against acrylamide-induced toxicity through its free radical scavenging and potent antioxidant activities.
      Citation: Biochemistry and Cell Biology
      PubDate: Mon, 01 Dec 2014 08:00:00 GMT
      DOI: 10.1139/bcb-2014-0122
  • Cardioprotective properties of citicoline against hyperthyroidism-induced
           reperfusion damage in rat hearts
    • Authors: Luz Hernández-Esquivel, Natalia Pavón, Mabel Buelna-Chontal, Héctor González-Pacheco, Javier Belmont, Edmundo Chávez
      Pages: 1 - 7
      Abstract: Biochemistry and Cell Biology, e-First Articles. Hyperthyroidism represents an increased risk factor for cardiovascular morbidity, especially when the heart is subjected to an ischemia/reperfusion process. The aim of this study was to explore the possible protective effect of the nucleotide citicoline on the susceptibility of hyperthyroid rat hearts to undergo reperfusion-induced damage, which is associated with mitochondrial dysfunction. Hence, we analyzed the protective effect of citicoline on the electrical behavior and on the mitochondrial function in rat hearts. Hyperthyroidism was established after a daily i.p. injection of triiodothyronine (at 2 mg/kg of body weight) during 5 days. Thereafter, citicoline was administered i.p. (at 125 mg/kg of body weight) for 5 days. In hyperthyroid rat hearts, citicoline protected against reperfusion-induced ventricular arrhythmias. Moreover, citicoline maintained the accumulation of mitochondrial Ca2+, allowing mitochondria to reach a high transmembrane electric gradient that protected against the release of cytochrome c. It also preserved the activity of the enzyme aconitase that inhibited the release of cytokines. The protection also included the inhibition of oxidative stress-induced mDNA disruption. We conclude that citicoline protects against the reperfusion damage that is found in the hyperthyroid myocardium. This effect might be due to its inhibitory action on the permeability transition in mitochondria.
      Citation: Biochemistry and Cell Biology
      PubDate: Tue, 18 Nov 2014 08:00:00 GMT
      DOI: 10.1139/bcb-2014-0116
  • Isolation of autophagosome subpopulations after induction of autophagy by
    • Authors: Xi Chen, Lin-Jie Li, Xiao-Yu Zheng, Hong-Qiang Shen, Shi-Qiang Shang
      Pages: 1 - 5
      Abstract: Biochemistry and Cell Biology, e-First Articles. Autophagy is a dynamic process accomplished by the generation and maturation of autophagosomes. Isolation of autophagosomes and subsequent compositional analysis can provide information about their biogenesis mechanism. In this article, HEK293 cells expressing GFP-LC3 were treated by calcium phosphate precipitates (CPP) to induce autophagy. The autophaogomes induced by CPP were tubular and vesicular structures, extensively formed in the cytosol. After all membranes in the cell lysate were fractionated by differential centrifugation, autophagosomes from light and heavy membranes were isolated by immuno-precipitation, using antibodies against GFP-LC3 and Atg5. We found that GFP-LC3 and Atg5 positive autophagosomes represented distinctive subpopulations. Judged from the molecular markers associated, including organelle markers and Atg proteins, GFP-LC3 positive autophagosomes were overall at the later biogenetic stage. Furthermore, both GFP-LC3 and Atg5 positive autophagosomes from light membranes were less mature than those from heavy membranes. We have established a method to isolate subpopulations of autophagsomes for further characterization.
      Citation: Biochemistry and Cell Biology
      PubDate: Thu, 13 Nov 2014 22:33:37 GMT
      DOI: 10.1139/bcb-2014-0115
  • New insights into lung development and diseases: the role of microRNAs
    • Authors: Dina Johar, Vinayakumar Siragam, Thomas H. Mahood, Richard Keijzer
      Pages: 1 - 10
      Abstract: Biochemistry and Cell Biology, e-First Articles. MicroRNAs (miRNAs) are short endogenous noncoding RNA molecules (∼22 nucleotides) that can regulate gene expression at the post-transcription level. Research interest in the role of miRNAs in lung biology is emerging. MiRNAs have been implicated in a range of processes such as development, homeostasis, and inflammatory diseases in lung tissues and are capable of inducing differentiation, morphogenesis, and apoptosis. In recent years, several studies have reported that miRNAs are differentially regulated in lung development and lung diseases in response to epigenetic changes, providing new insights for their versatile role in various physiological and pathological processes in the lung. In this review, we discuss the contribution of miRNAs to lung development and diseases and possible future implications in the field of lung biology.
      Citation: Biochemistry and Cell Biology
      PubDate: Fri, 07 Nov 2014 22:35:08 GMT
      DOI: 10.1139/bcb-2014-0103
  • Meeting report: The 57th Annual Meeting of the CSMB, Membrane Proteins in
           Health and Disease
    • Authors: Joseph R. Casey
      Pages: 1 - 2
      Abstract: Biochemistry and Cell Biology, e-First Articles.
      Citation: Biochemistry and Cell Biology
      PubDate: Thu, 30 Oct 2014 18:58:23 GMT
      DOI: 10.1139/bcb-2014-0131
  • A cis-acting element in the promoter of human ether à go-go 1
           potassium channel gene mediates repression by calcitriol in human cervical
           cancer cells
    • Authors: V. Cázares-Ordoñez, R.J. González-Duarte, L. Díaz, M. Ishizawa, S. Uno, V. Ortíz, M.L. Ordoñez-Sánchez, M. Makishima, F. Larrea, E. Avila
      Pages: 1 - 8
      Abstract: Biochemistry and Cell Biology, e-First Articles. The human ether à go-go 1 potassium channel (hEAG1) is required for cell cycle progression and proliferation of cancer cells. Inhibitors of hEAG1 activity and expression represent potential therapeutic drugs in cancer. Previously, we have shown that hEAG1 expression is downregulated by calcitriol in a variety of cancer cells. Herein, we provided evidence on the regulatory mechanism involved in such repressive effect in cells derived from human cervical cancer. Our results indicate that repression by calcitriol occurs at the transcriptional level and involves a functional negative vitamin D response element (nVDRE) E-box type in the hEAG1 promoter. The described mechanism in this work implies that a protein complex formed by the vitamin D receptor-interacting repressor, the vitamin D receptor, the retinoid X receptor, and the Williams syndrome transcription factor interact with the nVDRE in the hEAG1 promoter in the absence of ligand. Interestingly, all of these transcription factors except the vitamin D receptor-interacting repressor are displaced from hEAG1 promoter in the presence of calcitriol. Our results provide novel mechanistic insights into calcitriol mode of action in repressing hEAG1 gene expression.
      Citation: Biochemistry and Cell Biology
      PubDate: Wed, 22 Oct 2014 09:09:54 GMT
      DOI: 10.1139/bcb-2014-0073
  • Defining the identity of human adipose-derived mesenchymal stem cells
    • Authors: Elisa Montelatici, Barbara Baluce, Enrico Ragni, Cristiana Lavazza, Valentina Parazzi, Riccardo Mazzola, Giovanna Cantarella, Massimiliano Brambilla, Rosaria Giordano, Lorenza Lazzari
      Pages: 1 - 9
      Abstract: Biochemistry and Cell Biology, e-First Articles. Adipose-derived mesenchymal stem cells (ADMSCs) are an ideal population for regenerative medical application. Both the isolation procedure and the culturing conditions are crucial steps, since low yield can limit further cell therapies, especially when minimal adipose tissue harvests are available for cell expansion. To date, a standardized procedure encompassing both isolation sites and expansion methods is missing, thus making the choice of the most appropriate conditions for the preparation of ADMSCs controversial, especially in view of the different applications needed. In this study, we compared the effects of three different commercial media (DMEM, aMEM, and EGM2), routinely used for ADMSCs expansion, and two supplements, FBS and human platelet lysate, recently proven to be an effective alternative to prevent xenogeneic antibody transfer and immune alloresponse in the host. Notably, all the conditions resulted in being safe for ADMSCs isolation and expansion with platelet lysate supplementation giving the highest isolation and proliferation rates, together with a commitment for osteogenic lineage. Then, we proved that the high ADMSC hematopoietic supportive potential is performed through a constant and abundant secretion of both GCSF and SCF. In conclusion, this study further expands the knowledge on ADMSCs, defining their identity definition and offers potential options for in vitro protocols for clinical production, especially related to HSC expansion without use of exogenous cytokines or genetic modifications.
      Citation: Biochemistry and Cell Biology
      PubDate: Mon, 20 Oct 2014 21:38:21 GMT
      DOI: 10.1139/bcb-2014-0094
  • Non-genomic effects of spironolactone and eplerenone in cardiomyocytes of
           neonatal Wistar rats: do they evoke cardioprotective pathways'
    • Authors: Milla Marques Hermidorff, Gabriela de Oliveira Faria, Gabriela de Cassia Sousa Amâncio, Leonardo Vinícius Monteiro de Assis, Mauro César Isoldi
      Pages: 1 - 11
      Abstract: Biochemistry and Cell Biology, e-First Articles. Mineralocorticoid receptor (MR) antagonists of aldosterone (spironolactone and eplerenone) display beneficial effects in the treatment of cardiopathies; however, many of these responses are independent of this antagonism. The mechanisms of action of these drugs are not well known; few studies have comparatively evaluated whether eplerenone as well as spironolactone display cardioprotective effects independent of the blockade of aldosterone. To study these mechanisms, which lead to cardioprotective responses, and to evaluate comparatively their effects in vitro, we have evaluated the proliferative effect of spironolactone and eplerenone in primary culture of cardiomyocytes and fibroblasts of neonatal Wistar rats in the presence and absence of aldosterone. Spironolactone and eplerenone promoted proliferation of cardiomyocyte even in the absence of aldosterone, suggesting a signaling pathway independent of the antagonism over aldosterone. Spironolactone was able to reduce the proliferation of fibroblasts and to reverse the proliferation promoted by aldosterone, which was also displayed by eplerenone. To elucidate the biochemical pathways evoked by these drugs, we sought to analyze Ca2+, cAMP, and cGMP, and the activity of PKC and ERK1/2. Spironolactone and eplerenone increased the levels of Ca2+, cGMP and activity of ERK 1/2, and reversed the action of aldosterone on the activity of PKC and ERK1/2. Interestingly, only spironolactone increased the levels of cAMP. Our data support the fact that in addition to aldosterone, both spironolactone and eplerenone display rapid responses (non-genomic) such as an increase on cAMP, Ca2+, and cGMP by spironolactone, and Ca2+ and cGMP by eplerenone. We have observed a more consistent cardioprotection promoted by spironolactone; however, these effects have yet to be tested clinically. Therefore, our data show that these drugs do not only act as an antagonist of MR, but could lead to a new pharmacological classification of these drugs.
      Citation: Biochemistry and Cell Biology
      PubDate: Mon, 13 Oct 2014 21:37:13 GMT
      DOI: 10.1139/bcb-2014-0110
  • Epigenetic contributions to the developmental origins of adult lung
    • Authors: Lisa A. Joss-Moore, Robert H. Lane, Kurt H. Albertine
      Pages: 1 - 9
      Abstract: Biochemistry and Cell Biology, e-First Articles. Perinatal insults, including intrauterine growth restriction, preterm birth, maternal exposure to toxins, or dietary deficiencies produce deviations in the epigenome of lung cells. Occurrence of perinatal insults often coincides with the final stages of lung development. The result of epigenome disruptions in response to perinatal insults during lung development may be long-term structural and functional impairment of the lung and development of lung disease. Understanding the contribution of epigenetic mechanisms to life-long lung disease following perinatal insults is the focus of the developmental origins of adult lung disease field. DNA methylation, histone modifications, and microRNA changes are all observed in various forms of lung disease. However, the perinatal contribution to such epigenetic mechanisms is poorly understood. Here we discuss the developmental origins of adult lung disease, the interplay between perinatal events, lung development and disease, and the role that epigenetic mechanisms play in connecting these events.
      Citation: Biochemistry and Cell Biology
      PubDate: Mon, 13 Oct 2014 21:33:28 GMT
      DOI: 10.1139/bcb-2014-0093
  • O-GlcNAc protein modification in C2C12 myoblasts exposed to oxidative
           stress indicates parallels with endogenous antioxidant defense
    • Authors: Tina Tinkara Peternelj, Susan A. Marsh, Christudas Morais, David M. Small, Vincent J. Dalbo, Patrick S. Tucker, Jeff S. Coombes
      Pages: 1 - 11
      Abstract: Biochemistry and Cell Biology, e-First Articles. A growing body of evidence demonstrates the involvement of protein modification with O-linked β-N-acetylglucosamine (O-GlcNAc) in the stress response and its beneficial effects on cell survival. Here we investigated protein O-GlcNAcylation in skeletal muscle cells exposed to oxidative stress and the crosstalk with endogenous antioxidant system. The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. C2C12 myoblasts were subjected to 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, and the inhibitors of O-GlcNAc cycling enzymes. Surprisingly, O-GlcNAc levels were significantly increased only with glucosamine, whilst other treatments showed no effect. Significant changes at the mRNA level were observed with concomitant upregulation of the genes for O-GlcNAc enzymes and stress-related proteins with oxidizing agents and downregulation of these genes with agents promoting O-GlcNAcylation. Our findings suggest a role of O-GlcNAc in the stress response and indicate an inhibitory mechanism controlling O-GlcNAc levels in the muscle cells. This could represent an important homeostatic regulation of the cellular defense system.
      Citation: Biochemistry and Cell Biology
      PubDate: Wed, 08 Oct 2014 21:37:03 GMT
      DOI: 10.1139/bcb-2014-0106
  • The effects of a protein osmolyte on the stability of the integral
           membrane protein glycerol facilitator
    • Authors: Simon Baturin, Jamie J. Galka, Hadeesha Piyadasa, S. Gajjeraman, Joe D. O’Neil
      Pages: 1 - 12
      Abstract: Biochemistry and Cell Biology, e-First Articles. Osmolytes are naturally occurring molecules used by a wide variety of organisms to stabilize proteins under extreme conditions of temperature, salinity, hydrostatic pressure, denaturant concentration, and desiccation. The effects of the osmolyte trimethylamine N-oxide (TMAO) as well as the influence of detergent head group and acyl chain length on the stability of the Escherichia coli integral membrane protein glycerol facilitator (GF) tetramer to thermal and chemical denaturation by sodium dodecyl sulphate (SDS) are reported. TMAO promotes the association of the normally tetrameric α-helical protein into higher order oligomers in dodecyl-maltoside (DDM), but not in tetradecyl-maltoside (TDM), lyso-lauroylphosphatidyl choline (LLPC), or lyso-myristoylphosphatidyl choline (LMPC), as determined by dynamic light scattering (DLS); an octameric complex is particularly stable as indicated by SDS polyacrylamide gel electrophoresis. TMAO increases the heat stability of the GF tetramer an average of 10 °C in the 4 detergents and also protects the protein from denaturation by SDS. However, it did not promote re-association to the tetramer when added to SDS-dissociated protein. TMAO also promotes the formation of rod-like detergent micelles, and DLS was found to be useful for monitoring the structure of the protein and the redistribution of detergent during thermal dissociation of the protein. The protein is more thermally stable in detergents with the phosphatidylcholine head group (LLPC and LMPC) than in the maltoside detergents. The implications of the results for osmolyte mechanism, membrane protein stability, and protein–protein interactions are discussed.
      Citation: Biochemistry and Cell Biology
      PubDate: Tue, 07 Oct 2014 07:00:00 GMT
      DOI: 10.1139/bcb-2014-0076
  • Identification of transcription factors involved in the transcriptional
           regulation of the CXCL12 gene in rat pancreatic insulinoma Rin-5F cell
    • Authors: Jelena Marković, Aleksandra Uskoković, Nevena Grdović, Svetlana Dinić, Mirjana Mihailović, Jelena Arambašić Jovanović, Goran Poznanović, Melita Vidaković
      Pages: 1 - 9
      Abstract: Biochemistry and Cell Biology, e-First Articles. Diabetes is characterized by a deficit in the number of functional pancreatic β-cells. Understanding the mechanisms that stimulate neogenesis of β-cells should contribute to improved maintenance of β-cell mass. Chemokine CXCL12 has recently become established as a novel β-cell growth factor, however the mechanisms controlling its expression require clarification. We investigated the proteins involved in the transcriptional regulation of the rat β-cell CXCL12 gene (Cxcl12). Using the electrophoretic mobility shift assay and chromatin immunoprecipitation, we established the in vitro and in vivo binding of C/EBPβ, C/EBPα, STAT3, p53, FOXO3a, and HMG I/Y to the Cxcl12 promoter. Co-immunoprecipitation experiments revealed protein–protein interactions between YY1 and PARP-1, FOXO3a and PARP-1, Sp1 and PARP-1, p53 and PARP-1, C/EBPβ and PARP-1, YY1 and p53, YY1 and FOXO3a, p53 and FOXO3a, Sp1 and FOXO3a, C/EBPβ and FOXO3a, C/EBPα and FOXO3a, Sp1 and STAT3. Our data lay the foundation for research into the interplay of signaling pathways that determine the β-cell Cxcl12 expression profile.
      Citation: Biochemistry and Cell Biology
      PubDate: Mon, 29 Sep 2014 21:36:52 GMT
      DOI: 10.1139/bcb-2014-0104
  • Cortical cholinergic dysregulation as a long-term consequence of neonatal
    • Authors: T.R. Anju, C.S. Paulose
      Pages: 1 - 7
      Abstract: Biochemistry and Cell Biology, e-First Articles. Neonatal hypoglycemia limits the glucose supply to cells, affecting the function of brain due to its high energy demand. This can cause long-term consequences in brain function, leading to memory and cognitive deficits. The present study evaluated the cholinergic functional regulation in cerebral cortex of one month old rats exposed to neonatal hypoglycemia to understand the long-term effects of early life stress. Receptor binding and gene expression studies were done in the cerebral cortex to analyze the changes in total muscarinicreceptors, muscarinic M1, M2, M3 receptors, and the enzymes involved in acetylcholine metabolism, cholineacetyl transferase and acetylcholine esterase. Neonatal hypoglycemia decreased total muscarinic receptors (p < 0.001) with reduced muscarinic M1, M2, and M3 receptor genes (p < 0.001) in one month old rats. The reduction in acetylcholine metabolism is indicated by the downregulated cholineacetyl transferase, upregulated acetylcholine esterase, and decreased vesicular acetylcholine transporter expression. These alterations in cholinergic function in one month old rat brain indicates the longterm consequences of neonatal hypoglycemia in cortical function, which can contribute to the onset of many disease conditions in later stages of life.
      Citation: Biochemistry and Cell Biology
      PubDate: Thu, 18 Sep 2014 21:36:42 GMT
      DOI: 10.1139/bcb-2014-0035
  • The role of miR-29 in pulmonary fibrosis
    • Authors: Leah Cushing, Pingping Kuang, Jining Lü
      Pages: 1 - 10
      Abstract: Biochemistry and Cell Biology, e-First Articles. Pulmonary fibrosis is a pathological condition in which lungs become scarred due to the excess extracellular matrix (ECM) deposition and structural alterations in the interstitium of lung parenchyma. Many patients with interstitial lung diseases (ILDs) caused by long-term exposure to toxic substances, chronic infections, or autoimmune responses develop fibrosis. Etiologies for many ILDs are unknown, such as idiopathic pulmonary fibrosis (IPF), a devastating, relentless form of pulmonary fibrosis with a median survival of 2–3 years. Despite several decades of research, factors that initiate and sustain the fibrotic response in lungs remain unclear and there is no effective treatment to block progression of fibrosis. Here we summarize recent findings on the antifibrotic activity of miR-29, a small noncoding regulatory RNA, in the pathogenesis of fibrosis by regulating ECM production and deposition, and epithelial–mesenchymal transition (EMT). We also describe interactions of miR-29 with multiple profibrotic and inflammatory pathways. Finally, we review the antifibrotic activity of miR-29 in animal models of fibrosis and highlight miR-29 as a promising therapeutic reagent or target for the treatment of pulmonary fibrosis.
      Citation: Biochemistry and Cell Biology
      PubDate: Thu, 18 Sep 2014 21:36:33 GMT
      DOI: 10.1139/bcb-2014-0095
  • Discovery of novel membrane binding structures and functions
    • Authors: Irina Kufareva, Marc Lenoir, Felician Dancea, Pooja Sridhar, Eugene Raush, Christin Bissig, Jean Gruenberg, Ruben Abagyan, Michael Overduin
      Pages: 1 - 9
      Abstract: Biochemistry and Cell Biology, e-First Articles. The function of a protein is determined by its intrinsic activity in the context of its subcellular distribution. Membranes localize proteins within cellular compartments and govern their specific activities. Discovering such membrane-protein interactions is important for understanding biological mechanisms and could uncover novel sites for therapeutic intervention. We present a method for detecting membrane interactive proteins and their exposed residues that insert into lipid bilayers. Although the development process involved analysis of how C1b, C2, ENTH, FYVE, Gla, pleckstrin homology (PH), and PX domains bind membranes, the resulting membrane optimal docking area (MODA) method yields predictions for a given protein of known three-dimensional structures without referring to canonical membrane-targeting modules. This approach was tested on the Arf1 GTPase, ATF2 acetyltransferase, von Willebrand factor A3 domain, and Neisseria gonorrhoeae MsrB protein and further refined with membrane interactive and non-interactive FAPP1 and PKD1 pleckstrin homology domains, respectively. Furthermore we demonstrate how this tool can be used to discover unprecedented membrane binding functions as illustrated by the Bro1 domain of Alix, which was revealed to recognize lysobisphosphatidic acid (LBPA). Validation of novel membrane-protein interactions relies on other techniques such as nuclear magnetic resonance spectroscopy (NMR), which was used here to map the sites of micelle interaction. Together this indicates that genome-wide identification of known and novel membrane interactive proteins and sites is now feasible and provides a new tool for functional annotation of the proteome.
      Citation: Biochemistry and Cell Biology
      PubDate: Thu, 18 Sep 2014 07:00:00 GMT
      DOI: 10.1139/bcb-2014-0074
  • C/EBPβ regulates P2X7 receptor expression in response to glucose
           challenge in intestinal epithelial cells
    • Authors: Maude S. Bilodeau, Guillaume Arguin, Fernand-Pierre Gendron
      Pages: 1 - 9
      Abstract: Biochemistry and Cell Biology, e-First Articles. Activation of the ATP-dependent P2X7 receptor modulates glucose transport in intestinal epithelial cells through the downregulation of glucose transporter GLUT2. In the present study, we show that an increase in glucose concentration stimulates P2X7 receptor transcription via modulation of CCAAT/enhancer binding proteins (C/EBPs) α and β expression. The described human P2X7 receptor promoter region (GenBank Y12851) was cloned upstream of a luciferase reporter gene in pGL4.10 plasmid and used to determine whether C/EBPs, namely C/EBPα and C/EBPβ, are able to stimulate the transcription of P2X7 receptor. Results show that C/EBPβ was the main regulator of P2X7 receptor expression in response to a glucose challenge. Chromatin immunoprecipitation (ChIP) assays further revealed that C/EBPβ occupied the –213 to +6 nt P2X7 promoter region. Surprisingly, C/EBPα was also able to bind this region as revealed by ChIP assays, but without inducing receptor transcription. In fact, C/EBPα and the C/EBPβ-LIP isoform blocked the C/EBPβ-dependent regulation of P2X7 receptor transcription. These findings suggest that glucose is not only the major source of energy for cell function but may also act as a signaling molecule to stimulate the expression of regulatory proteins.
      Citation: Biochemistry and Cell Biology
      PubDate: Wed, 17 Sep 2014 07:00:00 GMT
      DOI: 10.1139/bcb-2014-0098
  • Multi-physiopathological consequences of the c.1392G>T CFTR mutation
           revealed by clinical and cellular investigations
    • Authors: Raed Farhat, Ayman El-Seedy, Kamal El-Moussaoui, Marie-Claude Pasquet, Catherine Adolphe, Eric Bieth, Jeanne Languepin, Isabelle Sermet-Gaudelus, Alain Kitzis, Véronique Ladevèze
      Pages: 1 - 10
      Abstract: Biochemistry and Cell Biology, e-First Articles. This study combines a clinical approach and multiple level cellular analyses to determine the physiopathological consequences of the c.1392G>T (p.Lys464Asn) CFTR exon 10 mutation, detected in a CF patient with a frameshift deletion in trans and a TG(11)T(5) in cis. Minigene experiment, with different TG(m)T(n) alleles, and nasal cell mRNA extracts were used to study the impact of c.1392G>T on splicing in both in cellulo and in vivo studies. The processing and localization of p.Lys464Asn protein were evaluated, in cellulo, by western blotting analyses and confocal microscopy. Clinical and channel exploration tests were performed on the patient to determine the exact CF phenotype profile and the CFTR chloride transport activity. c.1392G>T affects exon 10 splicing by inducing its complete deletion and encoding a frameshift transcript. The polymorphism TG(11)T(5) aggravates the effects of this mutation on aberrant splicing. Analysis of mRNA obtained from parental airway epithelial cells confirmed these in cellulo results. At the protein level the p.Lys464Asn protein showed neither maturated form nor membrane localization. Furthermore, the in vivo channel tests confirmed the absence of CFTR activity. Thus, the c.1392G>T mutation alone or in association with the TG repeats and the poly T tract revealed obvious impacts on splicing and CFTR protein processing and functionality. The c.[T(5); 1392G>T] complex allele contributes to the CF phenotype by affecting splicing and inducing a severe misprocessing defect. These results demonstrate that the classical CFTR mutations classification is not sufficient: in vivo and in cellulo studies of a possible complex allele in a patient are required to provide correct CFTR mutation classification, adequate medical counseling, and adapted therapeutic strategies.
      Citation: Biochemistry and Cell Biology
      PubDate: Wed, 17 Sep 2014 07:00:00 GMT
      DOI: 10.1139/bcb-2014-0042
  • Cytochrome P450 expression in mouse brain: specific isoenzymes involved in
           Phase I metabolizing system of porphyrinogenic agents in both microsomes
           and mitochondria
    • Authors: Jimena Lavandera, Silvina Ruspini, Alcira Batlle, Ana María Buzaleh
      Pages: 1 - 6
      Abstract: Biochemistry and Cell Biology, e-First Articles. Brain cytochrome P450 (CYP) metabolizes a variety of drugs to produce their pharmacological effects within the brain. We have previously observed that porphyrinogenic agents altered CYP levels in brain. The aim of this work was to further study the involvement of mice brain mitochondrial and microsomal Phase I drug metabolizing system when porphyrinogenic agents, such as Enflurane, Isoflurane, allylisopropylacetamide, veronal, ethanol, and Griseofulvin were administered. To this end, CYP2E1, CYP2B1, and CYP3A4 expression were measured. NADPH cytochrome P450 reductase (CPR) expression was also determined. Western Blots were performed in microsomes and mitochondria of whole brain. Some of the drugs studied altered expression mainly in microsomes. Chronic Isoflurane augmented mitochondrial isoform, although this anaesthetic diminished microsomal expression. Ethanol and topical Griseofulvin affected expression in microsomes but not in mitochondria. CYP2E1 mitochondrial activity was induced by acute Enflurane; while the activity of the microsomal protein was enhanced in alcoholised animals. Ethanol also induced CYP2E1 expression in microsomes, although Isoflurane provoked opposite effects in mitochondria and microsomes. Expression of CPR was also induced. Several reports support an emergent role of CYP enzymes in the pathogenesis of neurological disorders, so CYP response in brain could be one of the multiples factors influencing porphyria acute attacks.
      Citation: Biochemistry and Cell Biology
      PubDate: Wed, 17 Sep 2014 07:00:00 GMT
      DOI: 10.1139/bcb-2014-0088
  • Paracellular calcium transport across renal and intestinal epithelia
    • Authors: R. Todd Alexander, Juraj Rievaj, Henrik Dimke
      Pages: 1 - 14
      Abstract: Biochemistry and Cell Biology, e-First Articles. Calcium (Ca2+) is a key constituent in a myriad of physiological processes from intracellular signalling to the mineralization of bone. As a consequence, Ca2+ is maintained within narrow limits when circulating in plasma. This is accomplished via regulated interplay between intestinal absorption, renal tubular reabsorption, and exchange with bone. Many studies have focused on the highly regulated active transcellular transport pathways for Ca2+ from the duodenum of the intestine and the distal nephron of the kidney. However, comparatively little work has examined the molecular constituents creating the paracellular shunt across intestinal and renal epithelium, the transport pathway responsible for the majority of transepithelial Ca2+ flux. More specifically, passive paracellular Ca2+ absorption occurs across the majority of the intestine in addition to the renal proximal tubule and thick ascending limb of Henle’s loop. Importantly, recent studies demonstrated that Ca2+ transport through the paracellular shunt is significantly regulated. Therefore, we have summarized the evidence for different modes of paracellular Ca2+ flux across renal and intestinal epithelia and highlighted recent molecular insights into both the mechanism of secondarily active paracellular Ca2+ movement and the identity of claudins that permit the passage of Ca2+ through the tight junction of these epithelia.
      Citation: Biochemistry and Cell Biology
      PubDate: Wed, 17 Sep 2014 07:00:00 GMT
      DOI: 10.1139/bcb-2014-0061
  • Inhibitory effects of kaempferol on the invasion of human breast carcinoma
           cells by downregulating the expression and activity of matrix
    • Authors: Chenglin Li, Yuanwei Zhao, Dan Yang, Yanyan Yu, Hao Guo, Ziming Zhao, Bei Zhang, Xiaoxing Yin
      Pages: 1 - 12
      Abstract: Biochemistry and Cell Biology, e-First Articles. Matrix metalloproteinases (MMPs) have been regarded as major critical molecules assisting tumor cells during metastasis, for excessive ECM (ECM) degradation, and cancer cell invasion. In the present study, in vitro and in vivo assays were employed to examine the inhibitory effects of kaempferol, a natural polyphenol of flavonoid family, on tumor metastasis. Data showed that kaempferol could inhibit adhesion, migration, and invasion of MDA-MB-231 human breast carcinoma cells. Moreover, kaempferol led to the reduced activity and expression of MMP-2 and MMP-9, which were detected by gelatin zymography, real-time PCR, and western blot analysis, respectively. Further elucidation of the mechanism revealed that kaempferol treatment inhibited the activation of transcription factor activator protein-1 (AP-1) and MAPK signaling pathway. Moreover, kaempferol repressed phorbol-12-myristate-13-acetate (PMA)-induced MMP-9 expression and activity through suppressing the translocation of protein kinase Cδ (PKCδ) and MAPK signaling pathway. Our results also indicated that kaempferol could block the lung metastasis of B16F10 murine melanoma cells as well as the expression of MMP-9 in vivo. Taken together, these results demonstrated that kaempferol could inhibit cancer cell invasion through blocking the PKCδ/MAPK/AP-1 cascade and subsequent MMP-9 expression and its activity. Therefore, kaempferol might act as a therapeutic potential candidate for cancer metastasis.
      Citation: Biochemistry and Cell Biology
      PubDate: Fri, 12 Sep 2014 21:38:09 GMT
      DOI: 10.1139/bcb-2014-0067
  • Expression of polycystins and fibrocystin on primary cilia of lung cells
    • Authors: Qiaolin Hu, Yuliang Wu, Jingfeng Tang, Wang Zheng, Qian Wang, Drew Nahirney, Marek Duszyk, Shaohua Wang, Jian-Cheng Tu, Xing-Zhen Chen
      Pages: 1 - 8
      Abstract: Biochemistry and Cell Biology, e-First Articles. Mutations in polycystin-1, polycystin-2, or fibrocystin account for autosomal dominant or recessive polycystic kidney disease. Renal cystogenesis is linked to abnormal localization and function of these cystoproteins in renal primary cilia. They are also expressed in extrarenal tissues in which their functions are unclear. Here we found that human type-II alveolar epithelial A549, airway submucosal Calu-3 cells, and rat bronchioles contain primary or multiple cilia in which we detected these cystoproteins. At sub-confluency, polycystin-1 was expressed on plasma membrane, while polycystin-2 was localized to the ER of resting cells. Both polycystins were detected on the spindle and mid-body of mitotic cells, while fibrocystin was on centrosome throughout cell cycle. Polycystins and fibrocystin may participate in regulating mucociliary sensing and transport within pulmonary airways.
      Citation: Biochemistry and Cell Biology
      PubDate: Fri, 12 Sep 2014 07:00:00 GMT
      DOI: 10.1139/bcb-2014-0062
  • Conformational changes opening and closing the CFTR chloride channel:
           Insights from cysteine scanning mutagenesis
    • Authors: Yassine El Hiani, Paul Linsdell
      Pages: 1 - 8
      Abstract: Biochemistry and Cell Biology, e-First Articles. Cystic fibrosis, the most common lethal genetic disease affecting young people in North America, is caused by failure of the chloride ion channel known as CFTR (cystic fibrosis transmembrane conductance regulator). CFTR belongs to the large family of ATP-binding cassette (ABC) membrane transporters. In CFTR, ATP-driven events at the nucleotide-binding domains (NBDs) open and close a gate that controls chloride permeation. However, the conformational changes concomitant with opening and closing of the CFTR gate are unknown. Diverse techniques including substituted cysteine accessibility method, disulfide cross-linking, and patch-clamp recording have been used to explore CFTR channel structure. Here, we consider the architecture of both the open and the closed CFTR channel. We review how CFTR channel structure changes between the closed and the open channel conformations and portray the relative function of both cytoplasmic and vestigial gates during the gating cycle. Understanding how the CFTR channel gates chloride permeation is central for understanding how CFTR defects lead to CF. Such knowledge opens the door for novel ways to maximize CFTR channel activity in a CF setting.
      Citation: Biochemistry and Cell Biology
      PubDate: Fri, 12 Sep 2014 07:00:00 GMT
      DOI: 10.1139/bcb-2014-0038
  • Retinol dehydrogenases: Membrane-bound enzymes for the visual function
    • Authors: Mustapha Lhor, Christian Salesse
      Pages: 1 - 14
      Abstract: Biochemistry and Cell Biology, e-First Articles. Retinoid metabolism is important for many physiological functions, such as differenciation, growth, and vision. In the visual context, after the absorption of light in rod photoreceptors by the visual pigment rhodopsin, 11-cis retinal is isomerized to all-trans retinal. This retinoid subsequently undergoes a series of modifications during the visual cycle through a cascade of reactions occurring in photoreceptors and in the retinal pigment epithelium. Retinol dehydrogenases (RDHs) are enzymes responsible for crucial steps of this visual cycle. They belong to a large family of proteins designated as short-chain dehydrogenases/reductases. The structure of these RDHs has been predicted using modern bioinformatics tools, which allowed to propose models with similar structures including a common Rossman fold. These enzymes undergo oxidoreduction reactions, whose direction is dictated by the preference and concentration of their individual cofactor (NAD(H)/NADP(H)). This review presents the current state of knowledge on functional and structural features of RDHs involved in the visual cycle as well as knockout models. RDHs are described as integral or peripheral enzymes. A topology model of the membrane binding of these RDHs via their N- and (or) C-terminal domain has been proposed on the basis of their individual properties. Membrane binding is a crucial issue for these enzymes because of the high hydrophobicity of their retinoid substrates.
      Citation: Biochemistry and Cell Biology
      PubDate: Wed, 03 Sep 2014 07:00:00 GMT
      DOI: 10.1139/bcb-2014-0082
  • The study of vacuolar-type ATPases by single particle electron microscopy
    • Authors: Jianhua Zhao, John L. Rubinstein
      Pages: 1 - 7
      Abstract: Biochemistry and Cell Biology, e-First Articles. Nature’s molecular machines often work through the concerted action of many different protein subunits, which can give rise to large structures with complex activities. Vacuolar-type ATPases (V-ATPases) are membrane-embedded protein assemblies with a unique rotary catalytic mechanism. The dynamic nature and instability of V-ATPases make structural and functional studies of these enzymes challenging. Electron microscopy (EM) techniques, especially single particle electron cryomicroscopy (cryo-EM) and negative-stain EM, have provided extensive insight into the structure and function of these protein complexes. This minireview outlines what has been learned about V-ATPases using electron microscopy, highlights current challenges for their structural study, and discusses what cryo-EM will allow us to learn about these fascinating enzymes in the future.
      Citation: Biochemistry and Cell Biology
      PubDate: Wed, 03 Sep 2014 07:00:00 GMT
      DOI: 10.1139/bcb-2014-0086
  • MicroRNA-139-5p regulates C2C12 cell myogenesis through blocking
           Wnt/β-catenin signaling pathway
    • Authors: Lin Mi, Youlei Li, Qiangling Zhang, Chen Zhao, Ying Peng, Gongshe Yang, Xueli Zheng
      Pages: 1 - 8
      Abstract: Biochemistry and Cell Biology, e-First Articles. MicroRNAs (miRNAs) are novel and potent regulators in myogenesis. However, the molecular mechanisms that many miRNAs regulate myoblast proliferation and differentiation which are largely unknown. Here, we found that miR-139-5p increased during C2C12 myoblast proliferation, while presenting an inverse trend during C2C12 myoblast differentiation. Flow cytometry and EdU incorporation assay showed that miR-139-5p slowed down the growth of C2C12 cells. Additional study demonstrated that ectopic introduction of miR-139-5p into C2C12 cells blocked myoblast differentiation. Importantly, we demonstrated for the first time that Wnt1, which is associated with the Wnt/β-catenin signaling pathway, was a direct target of miR-139-5p. Moreover, we found that the expression level of Wnt1 was suppressed significantly (p < 0.01) by miR-139-5p, which triggered inhibition of Wnt/β-catenin signaling through upregulation of glycogen synthase kinase 3 beta (GSK-3β; p < 0.05) and downregulation of p-GSK-3β (p < 0.01), β-catenin (p < 0.05), and nuclear β-catenin (p < 0.01). Taken together, these results suggest that miR-139-5p is an important negative regulator in myogenesis through blocking the Wnt1-mediated Wnt/β-catenin signaling pathway.
      Citation: Biochemistry and Cell Biology
      PubDate: Tue, 02 Sep 2014 22:00:30 GMT
      DOI: 10.1139/bcb-2014-0079
  • Acid-base transport in pancreatic cancer: Molecular mechanisms and
           clinical potential
    • Authors: Su Chii Kong, Andrea Gianuzzo, Ivana Novak, Stine Falsig Pedersen
      Pages: 1 - 11
      Abstract: Biochemistry and Cell Biology, e-First Articles. Solid tumors are characterized by a microenvironment that is highly acidic, while intracellular pH (pHi) is normal or even elevated. This is the result of elevated metabolic rates in the highly proliferative cancer cells, in conjunction with often greatly increased rates of net cellular acid extrusion. Studies in various cancers have suggested that while the acid extrusion mechanisms employed are generally the same as those in healthy cells, the specific transporters upregulated vary with the cancer type. The main such transporters include Na+/H+ exchangers, various HCO3− transporters, H+ pumps, and lactate-H+ cotransporters. The mechanisms leading to their dysregulation in cancer are incompletely understood but include changes in transporter expression levels, trafficking and membrane localization, and posttranslational modifications. In turn, accumulating evidence has revealed that in addition to supporting their elevated metabolic rate, their increased acid efflux capacity endows the cancer cells with increased capacity for invasiveness, proliferation, and chemotherapy resistance. The pancreatic duct exhibits an enormous capacity for acid-base transport, rendering pHi dysregulation a potentially very important topic in pancreatic ductal adenocarcinoma (PDAC). PDAC — accounting for about 90% of all pancreatic cancers — has one of the highest cancer mortality rates known, and new diagnostic and treatment options are highly needed. However, very little is known about whether pH regulation is altered in PDAC and, if so, the possible role of this in cancer development. Here, we review current models for pancreatic acid-base transport and pH homeostasis and summarize current views on acid-base dysregulation in cancer, focusing where possible on the few studies to date in PDAC. Finally, we present new data-mining analyses of acid-base transporter expression changes in PDAC and discuss essential directions for future work.
      Citation: Biochemistry and Cell Biology
      PubDate: Tue, 26 Aug 2014 07:00:00 GMT
      DOI: 10.1139/bcb-2014-0078
  • The transient receptor potential cation channel subfamily V member 6
           (TRPV6): Genetics, biochemical properties, and functions of exceptional
           calcium channel proteins
    • Authors: Christof Stoerger, Veit Flockerzi
      Pages: 1 - 8
      Abstract: Biochemistry and Cell Biology, e-First Articles. The transient receptor potential cation channel subfamily V member 6 (TRPV6) gene and cDNA were identified 15 years ago and exceptional observations on TrpV6 proteins and their function as a Ca2+-selective cation channel have been made since then. In this review we will summarize recent studies regarding the genetics, biochemical properties, and physiological functions of murine and human TrpV6 channel proteins. We will focus on TRPV6 gene polymorphisms, the start of TRPV6 translation at a non-AUG codon and the functions of TRPV6 in intestinal Ca2+ uptake, sperm maturation, and male fertility.
      Citation: Biochemistry and Cell Biology
      PubDate: Tue, 26 Aug 2014 07:00:00 GMT
      DOI: 10.1139/bcb-2014-0063
  • Functional role of arginine 425 in the mammalian Na+/H+ exchanger
    • Authors: Xiuju Li, Yike Ma, Larry Fliegel
      Pages: 1 - 6
      Abstract: Biochemistry and Cell Biology, e-First Articles. Na+/H+ exchanger isoform 1 (NHE1) is the principal plasma membrane Na+/H+ exchanger of mammalian cells and functions by exchanging one intracellular proton for one extracellular sodium ion. Critical transmembrane segments of Na+/H+ exchangers have discontinuous transmembrane helices, which result in a dipole within the membrane. Amino acid R425 has been suggested to play an important role in neutralizing one such helix dipole. To investigate this hypothesis, R425 was mutated to alanine, glutamine, histidine, or lysine and the mutant NHE1 proteins were expressed and characterized in NHE1-deficient cells. The R425A and R425E mutants exhibited complete loss of expression of mature, fully glycosylated NHE1, reduced expression overall, and greatly reduced cell surface targeting. The cell surface targeting, expression, and activity of the R425H and R425K mutant proteins were also impaired, though residual NHE1 activity remained. When reduced targeting and expression were accounted for, the R425H and R425K mutant proteins had activity similar to that of the wild-type protein. The results suggest that R425 is critical for NHE1 expression, targeting, and activity and that replacement with another basic residue can rescue activity. The findings are consistent with a role for R425 in both neutralizing a helix dipole and maintaining NHE1 structure and function.
      Citation: Biochemistry and Cell Biology
      PubDate: Thu, 21 Aug 2014 07:00:00 GMT
      DOI: 10.1139/bcb-2014-0070
  • PANC-1 cells proliferative response to ionizing radiation is related to
           GSK-3β phosphorylation
    • Authors: Nora A. Mohamad, Graciela P. Cricco, Claudia M. Cocca, Elena S. Rivera, Rosa M. Bergoc, Gabriela A. Martín
      Pages: 1 - 12
      Abstract: Biochemistry and Cell Biology, e-First Articles. Radiotherapy may be used to treat pancreatic cancer and relieve pain. We have previously reported that histamine modulates pancreatic adenocarcinoma PANC-1 cell proliferation. This work was aimed to evaluate whether histamine improves radiosensitivity of PANC-1 cells in relation to phosphorylation/inhibition of glycogen synthase kinase-3β (GSK-3β). Immediately after γ irradiation, intracellular hydrogen peroxide was markedly decreased together with a rapid increase in catalase activity. Although histamine diminished catalase activity in nonirradiated cells, it only partially hindered the increase observed in irradiated cells and could not modify radiosensitivity. In control cells, a high expression of total and a very low expression of phosphorylated/inactive GSK-3β were found. An increment in reactive oxygen species levels produced an augmentation in GSK-3β phosphorylation and suppressed cell proliferation. In both control and histamine-treated irradiated cells, the rise in catalase activity lowered reactive oxygen species levels and only a small increase in phosphorylated GSK-3β was detected. Alternatively, 3-aminotriazole, an irreversible inhibitor of catalase, reduced the survival fraction in irradiated control cells along with an increment in phosphorylated GSK-3β. These results suggest that upon irradiation, early catalase activation may be responsible for keeping GSK-3β active conceding cells a survival advantage toward cytotoxic effects of ionizing radiation.
      Citation: Biochemistry and Cell Biology
      PubDate: Sun, 25 Nov 2012 15:55:27 GMT
      DOI: 10.1139/bcb-2012-032
  • Utp22p acts in concert with Utp8p to channel aminoacyl-tRNA from the
           nucleolus to the nuclear tRNA export receptor Los1p but not Msn5p
    • Authors: Manoja B.K. Eswara, Ashley Clayton, Dev Mangroo
      Pages: 1 - 19
      Abstract: Biochemistry and Cell Biology, e-First Articles. Utp8p is an essential nucleolar protein that channels aminoacyl-tRNAs from aminoacyl-tRNA synthetases in the nucleolus to the nuclear tRNA export receptors located in the nucleoplasm and nuclear pore complex in Saccharomyces cerevisiae. Utp8p is also part of the U3 snoRNA-associated protein complex involved in 18S rRNA biogenesis in the nucleolus. We report that Utp22p, which is another member of the U3 snoRNA-associated protein complex, is also an intranuclear component of the nuclear tRNA export machinery. Depletion of Utp22p results in nuclear retention of mature tRNAs derived from intron-containing and intronless precursors. Moreover, Utp22p copurifies with the nuclear tRNA export receptor Los1p, the aminoacyl-tRNA synthetase Tys1p and Utp8p, but not with the RanGTPase Gsp1p and the nuclear tRNA export receptor Msn5p. Utp22p interacts directly with Utp8p and Los1p in a tRNA-independent manner in vitro. Utp22p also interacts directly with Tys1p, but this binding is stimulated when Tys1p is bound to tRNA. However, Utp22p, unlike Utp8p, does not bind tRNA saturably. These data suggest that Utp22p recruits Utp8p to aminoacyl-tRNA synthetases in the nucleolus to collect aminoacyl-tRNA and then accompanies the Utp8p–tRNA complex to deliver the aminoacyl-tRNAs to Los1p but not Msn5p. It is possible that Nrap/Nol6, the mammalian orthologue of Utp22p, plays a role in channelling aminoacyl-tRNA to the nuclear tRNA export receptor exportin-t.
      Citation: Biochemistry and Cell Biology
      PubDate: Tue, 20 Nov 2012 13:45:45 GMT
      DOI: 10.1139/bcb-2012-034
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