The proposed research, which was stimulated by the finding of decreased glutathione (GSH) levels in peripheral blood mononuclear cells and plasma of patients who are seropositive for HIV infection, and by independent studies which indicate that glutathione is required for T-lymphocyte proliferation, have the following specific aims: (I) To elucidate the properties of GSH that are involved in cellular proliferation and that may be involved in virus production, (II) To examine the synthesis and utilization of GSH by normal and HIV-infected cells, and (III) To study the effects of modulation of cellular GSH on the toxicity of certain drugs used in therapy of AIDS. These investigations are expected to form a necessary background of information required for possible therapy of HIV-infection by using approaches that increase cellular levels of GSH. Such therapy may consist of administration of (a) cysteine precursors, (b) gamma-glutamylcysteine or its precursors, (c) glutathione, or (d) glutathione derivatives such as glutathione monoesters. Approaches (a), (b) , and (c) require that the cellular catalysts necessary for GSH synthesis (gamma-glutamylcysteine synthetase and glutathione synthetase) are functional and that cellular energy is available. Approach (c) also requires the activity of gamma-glutamyl transpeptidase. On the other hand, approach (d) in which GSH mono esters are applied does not require cellular energy or the enzymes involved in GSH metabolism.
| Kruse, P; Anderson, M E; Loft, S (2001) Minor role of oxidative stress during intermediate phase of acute pancreatitis in rats. Free Radic Biol Med 30:309-17 |
| Anderson, M E (1998) Glutathione: an overview of biosynthesis and modulation. Chem Biol Interact 111-112:1-14 |
| Anderson, M E (1997) Glutathione and glutathione delivery compounds. Adv Pharmacol 38:65-78 |
| Huang, C S; He, W; Meister, A et al. (1995) Amino acid sequence of rat kidney glutathione synthetase. Proc Natl Acad Sci U S A 92:1232-6 |
| Ikeda, Y; Fujii, J; Anderson, M E et al. (1995) Involvement of Ser-451 and Ser-452 in the catalysis of human gamma-glutamyl transpeptidase. J Biol Chem 270:22223-8 |
| Levy, E J; Anderson, M E; Meister, A (1994) Preparation and properties of glutathione diethyl ester and related derivatives. Methods Enzymol 234:499-504 |
| Levy, E J; Anderson, M E; Meister, A (1993) Transport of glutathione diethyl ester into human cells. Proc Natl Acad Sci U S A 90:9171-5 |
