Transport of glutathione diethyl ester into human cells.
Glutathione monoesters in which the carboxyl group of the glycine residue is esterified were previously found, in contrast to glutathione itself, to be effectively transported into various types of cells and to be converted intracellularly into glutathione. Glutathione monoesters are thus useful for prevention of oxidative stress, certain toxicities, and for treatment of glutathione deficiency. Glutathione diethyl ester is rapidly split to the glutathione monoethyl ester by mouse plasma glutathione diester alpha-esterase activity. Thus, as expected, glutathione mono- and diesters have similar effects on cellular glutathione levels in mice. However, human plasma lacks glutathione diester alpha-esterase; thus, it became of interest to compare the transport properties of glutathione mono- and diesters in human cells. We found that human cells (erythrocytes, peripheral blood mononuclear cells, fibroblasts, ovarian tumor cells, and purified T cells) transport glutathione diethyl ester much more effectively than the corresponding monoethyl (glycyl) ester. Human cells rapidly convert glutathione diethyl ester to the monoester, whose intracellular levels rise to levels that are significantly higher than levels found after application of the monoester to the cells. High levels of the monoester provide the cells with a means of producing glutathione over a period of time. We conclude that glutathione diethyl ester is highly effective as a delivery agent for glutathione monoester, and thus for glutathione, in human cells and therefore could serve to decrease oxidative stress and toxicity. Hamster (and certain other animals) also lack plasma glutathione diester alpha-esterase and therefore would be suitable animal models. Previously reported toxicity of certain glutathione ester preparations appears to reflect the presence of impurities rather than effects of the esters.
Levy
E J
EJ
Department of Biochemistry, Cornell University Medical College, New York, NY 10021.
Anderson
M E
ME
Meister
A
A
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002460:Cell Line; D006224:Cricetinae; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008954:Models, Biological; D010051:Ovarian Neoplasms / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D014407:Tumor Cells, Cultured
C083627:glutathione diethyl ester; D005978:Glutathione