| Oxidative stress mediates apoptotic changes induced by hyperglycemia in human tubular kidney cells. | |
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MedLine Citation:
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PMID: 14684680 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Reactive oxygen species (ROS) are important mediators for several biologic responses, including apoptosis. The present study evaluated the time course of changes in intracellular ROS production and apoptosis-related proteins, as well as apoptotic changes in human tubular proximal cells (HK-2 cells) exposed to hyperglycemia. Apoptosis (annexin V binding), ROS formation (fluorescence probe dichlorofluorescin diacetate and FACScan flow cytometry), and X chromosome-linked protein (XIAP; Western blot) were studied in HK-2 cells grown in a medium containing normal (NG) or high glucose (HG) concentrations (5.5 or 30 mM, respectively) for 18 to 48 h. HG promoted an increase (65% at 18 h and 73% at 24 h; P < 0.05 versus NG) in intracellular ROS generation. At 18 h, the NF-kB binding activity (evaluated by electrophoretic mobility-shift assay) was suppressed by HG. At the same time, the expression of NF-kB-induced antiapoptotic XIAP was reduced in HG-treated cells. Apoptotic changes were observed at 48 h (34 +/- 7% in HG versus 10 +/- 3% in NG; P < 0.001). Changes in ROS production at 24 h predicted changes in the apoptotic index at 48 h (r = 0.96, P < 0.0001). These results suggest that hyperglycemia induces apoptotic changes in human tubular cells via an increase in oxidative stress and that a downregulation of antiapoptotic protein XIAP is a component of this response. |
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Authors:
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Daniela Verzola; Maria Bianca Bertolotto; Barbara Villaggio; Luciano Ottonello; Franco Dallegri; Francesca Salvatore; Valeria Berruti; Maria Teresa Gandolfo; Giacomo Garibotto; Giacomo Deferrari |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of the American Society of Nephrology : JASN Volume: 15 Suppl 1 ISSN: 1046-6673 ISO Abbreviation: J. Am. Soc. Nephrol. Publication Date: 2004 Jan |
Date Detail:
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Created Date: 2003-12-19 Completed Date: 2004-05-25 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9013836 Medline TA: J Am Soc Nephrol Country: United States |
Other Details:
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Languages: eng Pagination: S85-7 Citation Subset: IM |
Affiliation:
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Division of Nephrology, Department of Internal Medicine, University of Genoa, Genoa, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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physiology* Cells, Cultured Humans Hyperglycemia / metabolism* Kidney Tubules, Proximal / cytology*, metabolism* Oxidative Stress* Reactive Oxygen Species / metabolism* Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Reactive Oxygen Species |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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