Protection from reoxygenation injury by inhibition of rac1

Kyung Soo Kim, Kazuyo Takeda, Rachna Sethi, John B. Pracyk, Koichi Tanaka, Yi Fu Zhou, Zu Xi Yu, Victor J. Ferrans, Joseph T. Bruder, Imre Kovesdi, Kaikobad Irani, Pascal Goldschmidt-Clermont, Toren Finkel

Research output: Contribution to journalArticle

134 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1821-1826
Number of pages6
JournalJournal of Clinical Investigation
Volume101
Issue number9
StatePublished - May 1 1998
Externally publishedYes

Fingerprint

Reactive Oxygen Species
Wounds and Injuries
Vascular Smooth Muscle
Smooth Muscle Myocytes
Cell Death
rac GTP-Binding Proteins
ras Genes
Reperfusion Injury
Oxidants
Muscle Cells
Genes
Endothelial Cells
Fibroblasts

Keywords

  • Adenovirus
  • Rac
  • Ras
  • Reoxygenation
  • Signal transduction

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kim, K. S., Takeda, K., Sethi, R., Pracyk, J. B., Tanaka, K., Zhou, Y. F., ... Finkel, T. (1998). Protection from reoxygenation injury by inhibition of rac1. Journal of Clinical Investigation, 101(9), 1821-1826.

Protection from reoxygenation injury by inhibition of rac1. / Kim, Kyung Soo; Takeda, Kazuyo; Sethi, Rachna; Pracyk, John B.; Tanaka, Koichi; Zhou, Yi Fu; Yu, Zu Xi; Ferrans, Victor J.; Bruder, Joseph T.; Kovesdi, Imre; Irani, Kaikobad; Goldschmidt-Clermont, Pascal; Finkel, Toren.

In: Journal of Clinical Investigation, Vol. 101, No. 9, 01.05.1998, p. 1821-1826.

Research output: Contribution to journalArticle

Kim, KS, Takeda, K, Sethi, R, Pracyk, JB, Tanaka, K, Zhou, YF, Yu, ZX, Ferrans, VJ, Bruder, JT, Kovesdi, I, Irani, K, Goldschmidt-Clermont, P & Finkel, T 1998, 'Protection from reoxygenation injury by inhibition of rac1', Journal of Clinical Investigation, vol. 101, no. 9, pp. 1821-1826.
Kim KS, Takeda K, Sethi R, Pracyk JB, Tanaka K, Zhou YF et al. Protection from reoxygenation injury by inhibition of rac1. Journal of Clinical Investigation. 1998 May 1;101(9):1821-1826.
Kim, Kyung Soo ; Takeda, Kazuyo ; Sethi, Rachna ; Pracyk, John B. ; Tanaka, Koichi ; Zhou, Yi Fu ; Yu, Zu Xi ; Ferrans, Victor J. ; Bruder, Joseph T. ; Kovesdi, Imre ; Irani, Kaikobad ; Goldschmidt-Clermont, Pascal ; Finkel, Toren. / Protection from reoxygenation injury by inhibition of rac1. In: Journal of Clinical Investigation. 1998 ; Vol. 101, No. 9. pp. 1821-1826.
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