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

FEBS Letters

Han, Song Iy²  Kang, Ho Sung²  Shin, Eun Ah²  Kim, Jae-Hong¹  Kim, Kyung Hee²  Ha, Kwon Soo³  Kim, Han Do²  Kang, Kwang Il² 

[1] Laboratory of Molecular and Cellular Genetics, Institute of Environmental and Life Science, Hallym University, Chun-Cheon, Kangwon-do 200-702, South Korea;Department of Molecular Biology, College of Natural Sciences, Pusan National University, Pusan 609-735, South Korea;Biomolecular Research Group, Korea Basic Science Institute, Taejon 305-333, South Korea

关键词: Arachidonic acid;    Rac1;    Stress-activated protein kinase/c-Jun N-terminal kinase;    Membrane ruffling;    Hydrogen peroxide;   

DOI  :  10.1016/S0014-5793(99)00657-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown