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 H/sub 2/O/sub 2/-induced injury.
- Research Organization:
- Veterans Administration Medical Center, New York, NY (USA)
- OSTI ID:
- 5900750
- Journal Information:
- J. Appl. Physiol.; (United States), Vol. 66:3
- Country of Publication:
- United States
- Language:
- English
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ENZYME INHIBITORS
BIOCHEMICAL REACTION KINETICS
GLUTATHIONE
BIOSYNTHESIS
HYDROGEN PEROXIDE
TOXICITY
CATTLE
CELL CULTURES
ENDOTHELIUM
INHIBITION
ANIMAL TISSUES
ANIMALS
BODY
DOMESTIC ANIMALS
DRUGS
HYDROGEN COMPOUNDS
KINETICS
MAMMALS
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PEPTIDES
PEROXIDES
POLYPEPTIDES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
REACTION KINETICS
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SYNTHESIS
TISSUES
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology