| Type 1 diabetes affects topoisomerase I activity and GlcNAcylation in rat organs: kidney liver and pancreas. | |
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MedLine Citation:
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PMID: 22247452 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Chronic hyperglycemia leads to the development of diabetes-induced organs complications, through changes in genes expression and proteins function. We previously showed that in cell lines topoisomerase I (topo I), is modified by O- GlcNAcylation, which affects its DNA relaxation activity. Since topo-I participates in gene expression processes, we assumed that high glucose levels, will affect its regulation and activity. Here we examined the effect of hyperglycemia on the regulation, GlcNAcylation and activity of topo I, in various internal rat organs that were subjected to diabetes induced complications. Type 1 diabetes was induced in female rats by Streptozotocin injection. Topo I activity in nuclear protein extracts derived from diabetic and non-diabetic rat organs, and topo I mRNA level were examined. Topo I and O-GlcNac Transferase proteins and their O-GlcNAcylation were determined by Western blot and Immunoprecipitation assays. We show that topo I activity and enzyme protein level decreased in various tissues derived from the diabetic animals, while the enzyme mRNA level was not altered. Topo I protein was modified in vivo by O-GlcNAc, and O-GlcNAc Transferase was co-precipitated with topo I protein, suggesting a possible interaction between both enzymes. This study demonstrates , for the first time, that topo I activity is regulated by high glucose levels, as a result of the diabetic state and is modified in vivo by O-GlcNAcylation, suggesting that topo I, an essential enzyme for gene expression, is involved in cellular processes which may lead to the pathogenesis of diabetic complications. |
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Authors:
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Itzhak Levi; Yael Segev; Esther Priel |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-12 |
Journal Detail:
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Title: Glycobiology Volume: - ISSN: 1460-2423 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-16 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9104124 Medline TA: Glycobiology Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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The Shraga Segal Dept. of Microbiology& Immunology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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