Essential role of Rac GTPase in hydrogen peroxide-induced activation of c-fos serum response element.
In the present study, we investigated whether hydrogen peroxide activates c-fos serum response element (SRE) in Rat-2 fibroblast cells. By transient transfection analysis, exogenous H2O2 stimulated SRE-dependent reporter gene activity in a dose and time-dependent manner. Also, we examined the role of Rac GTPase and phospholipase A2 (PLA2) in the H2O2-induced SRE activation. Either transfection of a dominant negative Rac mutant, RacN17, plasmid or pretreatment of mepacrine, a potent inhibitor of PLA2, blocked H2O2-induced SRE activation dramatically. Together, these findings suggest a critical role of 'Rac and subsequent activation of phospholipase A2' in the signaling pathway of H2O2 to SRE.
Kim
J H
JH
Laboratory of Molecular and Cellular Genetics, Institute of Environment and Life Science, Hallym University, Chun-Cheon, South Korea. jhkim@sun.hallym.ac.kr
Kwack
H J
HJ
Choi
S E
SE
Kim
B C
BC
Kim
Y S
YS
Kang
I J
IJ
Kumar
C C
CC
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D051381:Rats; D026362:Serum Response Factor; D015398:Signal Transduction
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D026362:Serum Response Factor; D006861:Hydrogen Peroxide; D010741:Phospholipases A; D054467:Phospholipases A2; D020558:GTP Phosphohydrolases