Modulation of endothelial GSH concentrations: effect of exogenous GSH and GSH monoethyl ester.
We studied the effects of exogenous glutathione (GSH) and GSH monoethyl ester (GSH-MEE) on the enhancement of endothelial GSH concentrations. The preparation of GSH-MEE used contained 91% GSH-MEE, approximately 9% GSH diethyl ester (GSH-DEE) and a trace amount of GSH. Both GSH and GSH-MEE markedly stimulated the intracellular concentrations of GSH in endothelial cells. GSH-MEE was more potent than GSH. The enhancement of endothelial GSH concentration by exogenous GSH was completely inhibited by buthionine sulfoximine (BSO), a potent inhibitor of gamma-glutamylcysteine synthase, or acivicin (AT-125), an inhibitor of gamma-glutamyl transpeptidase, suggesting that it was due to the extracellular breakdown and subsequent intracellular resynthesis of GSH. In contrast, the effect of GSH-MEE was largely resistant to BSO and acivicin, suggesting that it was primarily due to transport of GSH-MEE followed by intracellular hydrolysis. The GSH-MEE preparation, which contained 9% GSH-DEE, at concentrations of 2 mM or higher caused vacuolization of endothelial cells. The enhancement of GSH concentrations by exogenous GSH, but not by GSH-MEE, protected endothelial cells against H2O2-induced injury.
Tsan
M F
MF
Research Service, Veterans Administration Medical Center, New York.
White
J E
JE
Rosano
C L
CL
D000818:Animals; D019328:Buthionine Sulfoximine; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005978:Glutathione / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007555:Isoxazoles / Q000494:pharmacology; D007700:Kinetics; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D011651:Pulmonary Artery; D011837:Radiation-Protective Agents / Q000494:pharmacology*
D007555:Isoxazoles; D011837:Radiation-Protective Agents; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; C042431:S-ethyl glutathione; D006861:Hydrogen Peroxide; D005978:Glutathione; C006303:acivicin