| Regulation of GLUT4 expression in denervated skeletal muscle. | |
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MedLine Citation:
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PMID: 19321702 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Denervation by sciatic nerve resection causes decreased muscle glucose transporter 4 (GLUT4) expression, but little is known about the signaling events that cause this decrease. Experiments were designed to test the hypothesis that decreased GLUT4 expression in denervated muscle occurs because of decreased calcium/CaMK activity, which would then lead to decreased activation of the transcription factors myocyte enhancer factor 2 (MEF2) and GLUT4 enhancer factor (GEF), which are required for normal GLUT4 expression. GLUT4 mRNA was elevated in mice expressing constitutively active CaMK isoform IV (CaMKIV) and decreased by denervation. Denervation decreased GEF binding to the promoter and the content of GEF in the nucleus, but there was no change in either MEF2 binding or MEF2 protein content. Expression of a MEF2-dependent reporter gene did not change in denervated skeletal muscle. To determine the domains of the GLUT4 promoter that respond to denervation, transgenic mice expressing the chloramphenicol acetyl transferase (CAT) reporter gene driven by different lengths of the human GLUT4 promoter were denervated. Using several different promoter/reporter gene constructs, we found that all areas of the GLUT4 promoter were truncated or missing, except for the MEF2 binding domain and the basal promoter. All of the GLUT4 promoter/CAT reporter constructs evaluated responded normally to denervation. Our data lead us to conclude that decreased CaMK activity is not the reason for decreased GLUT4 content in denervated muscle and that negative control of GLUT4 expression is not mediated through the MEF2 or GEF-binding domains. These findings indicate that withdrawal of a GEF- or MEF2-dependent signal is not likely a major determinant of the denervation effect on GLUT4 expression. Thus, the response to denervation may be mediated by other elements present in the basal promoter of the GLUT4 gene. |
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Authors:
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Ellis B Jensen; Donghai Zheng; Robert A Russell; Rhonda Bassel-Duby; R Sanders Williams; Ann Louise Olson; G Lynis Dohm |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-03-25 |
Journal Detail:
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Title: American journal of physiology. Regulatory, integrative and comparative physiology Volume: 296 ISSN: 0363-6119 ISO Abbreviation: Am. J. Physiol. Regul. Integr. Comp. Physiol. Publication Date: 2009 Jun |
Date Detail:
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Created Date: 2009-05-21 Completed Date: 2009-07-02 Revised Date: 2010-09-23 |
Medline Journal Info:
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Nlm Unique ID: 100901230 Medline TA: Am J Physiol Regul Integr Comp Physiol Country: United States |
Other Details:
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Languages: eng Pagination: R1820-8 Citation Subset: IM |
Affiliation:
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Department of Biology, Viterbo University, La Crosse, Wisconsin, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Binding Sites Calcium-Calmodulin-Dependent Protein Kinase Type 4 / genetics, metabolism Chloramphenicol O-Acetyltransferase / genetics DNA-Binding Proteins / metabolism Down-Regulation Genes, Reporter Glucose Transporter Type 4 / genetics, metabolism* Humans Mice Mice, Inbred C57BL Mice, Transgenic Muscle Denervation Muscle, Skeletal / innervation, metabolism* Myogenic Regulatory Factors / genetics, metabolism Promoter Regions, Genetic RNA, Messenger / metabolism Sciatic Nerve / surgery Signal Transduction Transcription Factors / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01 DK046121/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA-Binding Proteins; 0/GLUT4 enhancer factor, mouse; 0/Glucose Transporter Type 4; 0/Myogenic Regulatory Factors; 0/RNA, Messenger; 0/SLC2A4 protein, human; 0/Transcription Factors; EC 2.3.1.28/Chloramphenicol O-Acetyltransferase; EC 2.7.11.17/Calcium-Calmodulin-Dependent Protein Kinase Type 4 |
| Comments/Corrections | |
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