Arachidonic acid induces the activation of the stress-activated protein kinase, membrane ruffling and H2O2 production via a small GTPase Rac1

Eun Ah Shin, Kyung Hee Kim, Song Iy Han, Kwon Soo Ha, Jae-Hong Kim, Kwang Il Kang, Han Do Kim, Ho Sung Kang

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Arachidonic acid (AA) is generated via Rac-mediated phospholipase A2 (PLA2) activation in response to growth factors and cytokines and is implicated in cell growth and gene expression. In this study, we show that AA activates the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in a time- and dose-dependent manner. Indomethacin and nordihydroguaiaretic acid, potent inhibitors of cyclooxygenase and lipoxygenase, respectively, did not exert inhibitory effects on AA-induced SAPK/JNK activation, thereby indicating that AA itself could activate SAPK/JNK. As Rac mediates SAPK/JNK activation in response to a variety of stressful stimuli, we examined whether the activation of SAPK/JNK by AA is mediated by Rac1. We observed that AA-induced SAPK/JNK activation was significantly inhibited in Rat2-Rac1N17 dominant-negative mutant cells. Furthermore, treatment of AA induced membrane ruffling and production of hydrogen peroxide, which could be prevented by Rac1N17. These results suggest that AA acts as an upstream signal molecule of Rac, whose activation leads to SAPK/JNK activation, membrane ruffling and hydrogen peroxide production. Copyright (C) 1999 Federation of European Biochemical Societies.

Original languageEnglish
Pages (from-to)355-359
Number of pages5
JournalFEBS Letters
Volume452
Issue number3
DOIs
Publication statusPublished - 1999 Jun 11
Externally publishedYes

Keywords

  • Arachidonic acid
  • Hydrogen peroxide
  • Membrane ruffling
  • Rac1
  • Stress-activated protein kinase/c-Jun N-terminal kinase

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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