NDLI: Arachidonic acid activates c-jun N-terminal kinase through NADPH oxidase in rabbit proximal tubular epithelial cells.

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Arachidonic acid activates c-jun N-terminal kinase through NADPH oxidase in rabbit proximal tubular epithelial cells.

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Arachidonic acid activates c-jun N-terminal kinase through NADPH oxidase in rabbit proximal tubular epithelial cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Cui, X. L. Douglas, J. G.
Description	Author Affiliation: Cui XL ( Department of Medicine, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, OH 44106-4982, USA.);
Abstract	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 microM arachidonic acid and plateaued at 30 microM. 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 H(2)O(2), 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.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	8
Volume Number	94
Language	English
Publisher	National Academy of Sciences
Publisher Date	1997-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Arachidonic Acid Pharmacology JNK Mitogen-Activated Protein Kinases Kidney Tubules Enzymology Mitogen-Activated Protein Kinase Kinases NADPH Oxidase Metabolism Protein Kinases Animals Cells, Cultured Enzyme Activation Drug Effects Epithelium MAP Kinase Kinase 4 Rabbits Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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