Cytoprotective effect of reduced glutathione in hydrogen peroxide-induced endothelial cell injury.
The kinetic effects of hydrogen peroxide (H2O2) on cultured endothelial cells isolated from bovine carotid artery were studied. The cytoprotective effects of glutathione (GSH) on H2O2-induced cell injury were also investigated. H2O2-induced a dose- and time-dependent cell injury in cultured endothelial cells. H2O2-induced cell injury was blocked by simultaneous treatment by catalase, but not by superoxide dismutase. H2O2 also induced endogenous PGI2 biosynthesis, and the maximum PGI2 production was reached after 1 h treatment. Stimulation of PGI2 production was parallel with arachidonate release from H2O2-treated cells. However the prostaglandin biosynthesis enzyme activity in cells was inhibited by H2O2 treatment. When the cells were treated with GSH, the intracellular GSH reached a plateau after 3 h treatment. Both H2O2-induced cell injury and PGI2 production were significantly inhibited by the 3 h pretreatment with GSH. The cytoprotective effect of GSH was completely inhibited by buthionine sulfoximine which is a specific inhibitor of gamma-glutamylcysteine synthetase. The results indicate that the cytoprotective effect of GSH on H2O2-induced cell injury in cultured bovine carotid artery endothelial cells depends on the increase in intracellular GSH content.
Chen
S H
SH
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China.
Wu
H L
HL
Lin
M T
MT
Jen
C J
CJ
Wing
L Y
LY
Lei
H Y
HY
Tsao
C J
CJ
Chang
W C
WC
D000818:Animals; D019328:Buthionine Sulfoximine; D002374:Catalase / Q000494:pharmacology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis; D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors; D005978:Glutathione / Q000096:biosynthesis / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000633:toxicity*; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology
D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D006861:Hydrogen Peroxide; D011464:Epoprostenol; D002374:Catalase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione