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.