查看文章

To elucidate mechanisms underlying glutathione S-transferase p (GSTp)-mediated cellular protection against oxidative stress-induced cell death, the effect of GSTp on stress signaling pathways was investigated before and after H₂O₂ treatment. Under nonstressed conditions,increased expression of GSTp via a tet-off-inducible GSTp in NIH 3T3 cells increased the phosphorylation of mitogen-activated protein (MAP)kinase kinase 4, p38, extracellular receptor kinase (ERK), and inhibitor of κ-kinase (IKK), and reduced phosphorylation of MAP kinase kinase 7 and Jun NH₂-terminal kinase (JNK). Whereas H₂O₂ treatment of cells induced JNK, p38, and IKK activities, in the presence of H₂O₂ and elevated GSTp expression there was an additional increase in ERK, p38,and IKK activities and a decrease in JNK activity. GSTp-mediated protection from H₂O₂-induced death was attenuated upon inhibition of p38 …