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

FEBS Letters

Sies, Helmut¹  Klotz, Lars-Oliver¹  Schieke, Stefan M¹  Briviba, Karlis¹ 

[1] Institut für Physiologische Chemie I, Heinrich-Heine-Universität, Postfach 101007, D-40001 Düsseldorf, Germany

关键词: Peroxynitrite;    Signal transduction;    p38;    JNK1/2;    ERK1/2;    Selenoprotein;   

DOI  :  10.1016/S0014-5793(99)00372-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Peroxynitrite is a mediator of toxicity in pathological processes in vivo and causes damage by oxidation and nitration reactions. Here, we report a differential induction of mitogen-activated protein kinases (MAPKs) in WB-F344 rat liver epithelial cells by peroxynitrite. For the exposure of cultured cells with peroxynitrite, we employed a newly developed infusion method. At 6.5 μM steady-state concentration, the activation of p38 MAPK was immediate, while JNK1/2 and ERK1/2 were activated 60 min and 15 min subsequent to 3 min of exposure to peroxynitrite, respectively. Protein-bound 3-nitrotyrosine was detected. When cells were grown in a medium supplemented with sodium selenite (1 μM) for 48 h, complete protection was afforded against the activation of p38 and against nitration of tyrosine residues. These data suggest a new role for peroxynitrite in activating signal transduction pathways capable of modulating gene expression. Further, the abolition of the effects of peroxynitrite by selenite supplementation suggests a protective role of selenium-containing proteins.

【 授权许可】

Unknown