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 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 microM 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 microM) 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.
Schieke
S M
SM
Institut für Physiologische Chemie I, Heinrich-Heine-Universität, Düsseldorf, Germany.
Briviba
K
K
Klotz
L O
LO
Sies
H
H
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D004848:Epithelium / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide; D008099:Liver / Q000378:metabolism*; D009566:Nitrates / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D018038:Sodium Selenite / Q000494:pharmacology*; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D009566:Nitrates; C039642:peroxynitric acid; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D018038:Sodium Selenite