GSH role on platelet-derived growth factor receptor tyrosine phosphorylation induced by H2O2

This study, conducted on NIH3T3 cells, demonstrates that GSH depletion obta ined by buthionine sulfoximine (BSO) treatment does not affect platelet-der ived growth-factor receptor (PDGFr) autophosphorylation or cell protein pho sphorylation induced by exogenous addition of H2O2, while it does decrease tyrosine phosphorylation obtained by PDGF stimulation. This last effect see ms due to the lack of H2O2 generation; for the first time a relation betwee n intracellular GSH content and H2O2 production induced by PDGF has been de monstrated. Therefore, changes of GSH levels can affect the early events of the PDGFr signal pathways by redox regulation. It has also demonstrated th at in NIH3T3 cells, H2O2 can directly activate tyrosine phosphorylation by a reversible effect with the involvement of SH-group. This H2O2 effect is i ncreased by vanadate and by GSH depleting agent, diethylmaleate, which unli ke BSO is able to produce H2O2 as the current study shows. (C) 2001 Academi c Press.