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.
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China.
S H
SH
Chen
H L
HL
Wu
M T
MT
Lin
C J
CJ
Jen
L Y
LY
Wing
H Y
HY
Lei
C J
CJ
Tsao
W C
WC
Chang
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