Activation pattern of mitogen-activated protein kinases elicited by peroxynitrite: attenuation by selenite supplementation

Peroxynitrite is a mediator of toxicity in pathological processes in vivo a nd causes damage by oxidation and nitration reactions. Here, we report a di fferential induction of mitogen-activated protein kinases (MAPKs) in WB-F34 4 rat liver epithelial cells by peroxynitrite. For the exposure of cultured cells with peroxynitrite, we employed a newly developed infusion method. A t 6.5 mu M steady-state concentration, the activation of p38 MAPK was immed iate, while JNK1/2 and ERK1/2 were activated 60 min and 15 min subsequent t o 3 min of exposure to peroxynitrite, respectively. Protein-bound 3-nitroty rosine was detected. When cells were grown in a medium supplemented with so dium selenite (1 mu M) for 48 h, complete protection was afforded against t he activation of p38 and against nitration of tyrosine residues. These data suggest a new role for peroxynitrite in activating signal transduction pat hways capable of modulating gene expression. Further, the abolition of the effects of peroxynitrite by selenite supplementation suggests a protective role of selenium-containing proteins. (C) 1999 Federation of European Bioch emical Societies.