Protection from reoxygenation injury by inhibition of rac1.

Abstract	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
Journal	The Journal of clinical investigation (J Clin Invest) Vol. 101 Issue 9 Pg. 1821-6 (May 01 1998) ISSN: 0021-9738 [Print] United States
PMID	9576744 (Publication Type: Journal Article)
Chemical References	Free Radical Scavengers Reactive Oxygen Species Recombinant Proteins GTP-Binding Proteins rac GTP-Binding Proteins ras Proteins Oxygen
Topics	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)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!