Fas-mediated autophagy requires JNK activation in HeLa cells

Fas has been reported to play an important role in apoptosis: however, Fas-mediated autophagy and its mechanism are Still unclear. Here, we found that Fas agonistic antibody CH11-induced autophagy in HeLa cells, and inhibition of autophagy, by 3-MA increased CH11-induced apoptosis. A Fas antagonistic antibody (UB2) suppressed both CH11-induced autophagy and apoptosis. In addition, the CH11-induced autophagy was blocked by JNK inhibitor (SP600125), but it was not affected by caspase 8 inhibitor (Z-IETD); whereas the CH11-induced apoptosis was increased by SP600125, and it was suppressed by Z-IETD. Further experiments confirmed that JNK was activated by CH11 dose-dependently, and the activation Was Suppressed when autophagy was blocked by 3-MA. Together, our results suggest that JNK, but not caspase8,involves in Fas-mediated CH11-induced autophagy in HeLa cells, and this autophagy plays a protective role in CH11-induced cell death. (C) 2008 Elsevier Inc. All rights reserved.