Polypeptide from Chlamys farreri prevents UVA-induced HaCaT cells apoptosis partly through inhibition of caspase-8 pathway and mitochon- drial pathway

Polypeptide from Chlamys farreri prevents UVA-induced HaCaT cells apoptosis partly through inhibition of caspase-8 pathway and mitochondrial pathway B Li, B Ding, C Wang Medical College, Qingdao University, Qingdao, China Polypeptide from Chlamys farreri (PCF) is a novel marine active product isolated from the gonochoric Chinese scallop Chlamys farreri which has been recently found to be an effective antioxidant. In this study, we assessed the effect of PCF on UVAinduced intracellular signaling of apoptosis in HaCaT cells. Pretreatment with PCF significantly inhibited UVA-induced apoptosis in HaCaT cells. Pretreatment with the ROS scavenger N-acetylcysteine (NAC) and the caspase-8 inhibitor z-IETD-fmk and siRNA were found to effectively prevent UVA-induced apoptosis, suggesting that UVA-induced HaCaT cell apoptosis was partially due to generation of ROS and activation of the caspase-8 pathway. PCF strongly reduced the intracellular reactive oxygen species (ROS) level followed by inhibition the release of cytochrome c. The expression of CD95 and Fas-associating protein with death domain (FADD) was eliminated in a dose-dependent by PCF pretreatment in UVA-irradiated HaCaT cells, followed by inhibition of cleavage of procaspase-8 and procaspase-3, whose activation induced cell apoptosis. Consequently, the protective effect of PCF against UVA irradiation in HaCaT cells is exerted by suppression of generation of ROS followed by inhibition cytochrome c release and inactivation of Fas-FADDcaspase8caspase-3 pathway, resulting in blockage of UVA-induced apoptosis.