Arachidonic acid activates c-jun N-terminal kinase through NADPH oxidase in rabbit proximal tubular epithelial cells
AUTOR(ES)
Cui, Xiao-Lan
FONTE
The National Academy of Sciences of the USA
RESUMO
In kidney epithelial cells, arachidonic acid and other fatty acids are important signal transduction molecules for G protein-coupled receptors. We now demonstrate that arachidonic acid induced a time- and dose-dependent activation of JNK, a member of the mitogen-activated protein kinase family, as assessed by phosphorylation of the transcription factor ATF-2. Increments in JNK activity were detectable at 5 μM arachidonic acid and plateaued at 30 μM. Activation was specific to arachidonic acid and linoleic acid, since other fatty acids of the n − 3 and n − 6 series and/or various degrees of saturation were without effect. Specific inhibitors of cyclooxygenase-, lipoxygenase-, and cytochrome P450-dependent metabolism did not affect arachidonic acid-induced JNK activity. We further demonstrated that the free radical scavenger N-acetylcysteine blocked arachidonic acid-induced JNK activation, while H2O2, a reactive oxidative molecule, activated JNK in a dose-dependent manner, providing additional support for a redox mechanism. Moreover, arachidonic acid activated NADPH oxidase (EC 1.6.-.-, EC 1.6.99.-) in a dose-dependent manner, and the potency of superoxide generation paralleled that of JNK activation by other fatty acids. We conclude that in kidney epithelial cells arachidonic acid activates JNK by means of NADPH oxidase and superoxide generation, independent of eicosanoid biosynthesis.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=20516Documentos Relacionados
- Activation of c-Jun N-terminal kinase in bacterial lipopolysaccharide-stimulated macrophages.
- Angiotensin II stimulates calcium-dependent activation of c-Jun N-terminal kinase.
- The MLK Family Mediates c-Jun N-Terminal Kinase Activation in Neuronal Apoptosis
- TAK1 Participates in c-Jun N-Terminal Kinase Signaling during Drosophila Development
- Adenovirus E1B 19,000-Molecular-Weight Protein Activates c-Jun N-Terminal Kinase and c-Jun-Mediated Transcription