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 detoxification, can also play a part in cell proliferation events. Cell treatment with l-buthionine sulphoximine, which causes glutathione depletion, is accompanied by a decrease in cell proliferation. At present no precise relationship between this thiol and any critical intermediate of the mitogenic cascade has been proved. In this study, conducted on NIH/3T3 murine fibroblasts, we demonstrate a strict correlation between glutathione levels and platelet-derived growth-factor-receptor activation in response to stimulation and cell proliferation. The receptor autophosphorylation is severely impaired at low glutathione cellular levels. The interaction of glutathione with this growth-factor receptor in vivo, while being rather specific, is complex and may involve both cytosolic and extracellular receptor domains.
Rigacci
S
S
Department of Biochemical Sciences, University of Firenze, Viale Morgagni 50, 50134 Firenze, Italy.
Iantomasi
T
T
Marraccini
P
P
Berti
A
A
Vincenzini
M T
MT
Ramponi
G
G
D016475:3T3 Cells; D000818:Animals; D002455:Cell Division; D005978:Glutathione / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D015398:Signal Transduction
D010982:Platelet-Derived Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor; D005978:Glutathione