Document Detail


Oxidative stress mediates apoptotic changes induced by hyperglycemia in human tubular kidney cells.
MedLine Citation:
PMID:  14684680     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Daniela Verzola; Maria Bianca Bertolotto; Barbara Villaggio; Luciano Ottonello; Franco Dallegri; Francesca Salvatore; Valeria Berruti; Maria Teresa Gandolfo; Giacomo Garibotto; Giacomo Deferrari
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
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:
Created Date:  2003-12-19     Completed Date:  2004-05-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9013836     Medline TA:  J Am Soc Nephrol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  S85-7     Citation Subset:  IM    
Affiliation:
Division of Nephrology, Department of Internal Medicine, University of Genoa, Genoa, Italy.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / physiology*
Cells, Cultured
Humans
Hyperglycemia / metabolism*
Kidney Tubules, Proximal / cytology*,  metabolism*
Oxidative Stress*
Reactive Oxygen Species / metabolism*
Time Factors
Chemical
Reg. No./Substance:
0/Reactive Oxygen Species

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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