Implication of the small GTPase Rac1 in the apoptosis induced by UV in Rat-2 fibroblasts.
Exposure of mammalian cells to ultraviolet (UV) light elicits a cellular response and also lead to apoptotic cell death. However, the role of Rac, a member of Rho family GTPases, in the UV-induced apoptosis has never been examined. In UV-irradiated Rat-2 fibroblasts, nuclear fragmentation began to be observed within 2 h and the total viability of Rat-2 cells were only about 15% at 6 h following by UV irradiation, whereas the total viability in Rat2-Rac(N17) cells stably expressing RacN17, a dominant negative Rac1 mutant, was almost close to 67%. Pretreatment with SB203580, a specific inhibitor of p38 kinase, likewise attenuated UV-induced cell death, but PD98059, a MEK inhibitor, did not. Thus, Rac1 and p38 kinase appear to be components in the apoptotic signaling pathway induced by UV irradiation in Rat-2 fibroblasts. In addition, our results show that p38 kinase stimulation by UV is dramatically inhibited by RacN17, suggesting that p38 kinase is situated downstream of Rac1 in the UV signaling to apoptosis.
Eom
Y W
YW
Department of Life Science, Kwangju Institute of Science and Technology (K-JIST), Kwang-Ju 500-712, Korea.
Yoo
M H
MH
Woo
C H
CH
Hwang
K C
KC
Song
W K
WK
Yoo
Y J
YJ
Chun
J S
JS
Kim
J H
JH
D000818:Animals; D017209:Apoptosis; D006690:Bisbenzimidazole; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects*; D005456:Fluorescent Dyes; D005799:Genes, Dominant; D007093:Imidazoles / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009154:Mutation; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D014162:Transfection; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D007093:Imidazoles; D011725:Pyridines; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020830:rac1 GTP-Binding Protein; D006690:Bisbenzimidazole; C093642:SB 203580