EVIDENCE FOR GLUTATHIONE INVOLVEMENT IN PLATELET-DERIVED GROWTH-FACTOR-MEDIATED SIGNAL-TRANSDUCTION

Recent studies show that glutathione, while being involved in the well -known physiological processes of amino acid transport and detoxificat ion, can also play a part in cell proliferation events. Cell treatment with L-buthionine sulphoximine, which causes glutathione depletion, i s accompanied by a decrease in cell proliferation, At present no preci se relationship between this thiol and any critical intermediate of th e mitogenic cascade has been proved. In this study, conducted on NIH/3 T3 murine fibroblasts, we demonstrate a strict correlation between glu tathione levels and platelet-derived growth-factor-receptor activation in response to stimulation and cell proliferation. The receptor autop hosphorylation is severely impaired at low glutathione cellular levels . The interaction of glutathione with this growth-factor receptor in v ivo, while being rather specific, is complex and may involve both cyto solic and extracellular receptor domains.