Document Detail


Protection from reoxygenation injury by inhibition of rac1.
MedLine Citation:
PMID:  9576744     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We demonstrate that adenoviral-mediated gene transfer of a dominant negative rac1 gene product (N17rac1) inhibits the intracellular burst of reactive oxygen species (ROS) that occurs after reoxygenation of vascular smooth muscle cells. In contrast, expression of a dominant negative ras gene (N17ras) had no effect. Challenge of control cells and cells expressing N17rac1 with a direct oxidant stress produced an equivalent increase in intracellular ROS levels and subsequent cell death. This suggests that N17rac1 expression appears to block production of harmful oxygen radicals and does not act directly or indirectly to scavenge ROS generated during reoxygenation. Expression of N17rac1 results in protection from hypoxia/reoxygenation-induced cell death in a variety of cell types including vascular smooth muscle cells, fibroblasts, endothelial cells, and ventricular myocytes. These results suggest that reoxygenation injury requires the activation of rac proteins, and that inhibition of rac-dependent pathways may be a useful strategy for the prevention of reperfusion injury in ischemic tissues.
Authors:
K S Kim; K Takeda; R Sethi; J B Pracyk; K Tanaka; Y F Zhou; Z X Yu; V J Ferrans; J T Bruder; I Kovesdi; K Irani; P Goldschmidt-Clermont; T Finkel
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  101     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1998 May 
Date Detail:
Created Date:  1998-06-08     Completed Date:  1998-06-08     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1821-6     Citation Subset:  AIM; IM    
Affiliation:
Cardiology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
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MeSH Terms
Descriptor/Qualifier:
Aerobiosis
Anaerobiosis
Animals
Aorta / cytology
Cell Death / drug effects
Cells, Cultured
Free Radical Scavengers
GTP-Binding Proteins / antagonists & inhibitors*,  genetics
Humans
Muscle, Smooth, Vascular / drug effects*,  pathology
Oxygen / pharmacology*
Rats
Reactive Oxygen Species / metabolism
Recombinant Proteins / antagonists & inhibitors
Reperfusion Injury / prevention & control
Signal Transduction
Umbilical Veins / cytology
rac GTP-Binding Proteins
ras Proteins / metabolism
Chemical
Reg. No./Substance:
0/Free Radical Scavengers; 0/Reactive Oxygen Species; 0/Recombinant Proteins; 7782-44-7/Oxygen; EC 3.6.1.-/GTP-Binding Proteins; EC 3.6.5.2/rac GTP-Binding Proteins; EC 3.6.5.2/ras Proteins
Comments/Corrections

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


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