Li Bing-Hua, Zhou Ying-Bin, Guo Shen-Bo, Wang Chun-bo
Department of Pharmacology, Medical College, Qingdao University, Qingdao, Shandong 266021, China.
Free Radic Res. 2007 Nov;41(11):1224-32. doi: 10.1080/10715760701636858.
Polypeptide from Chlamys farreri (PCF) is a novel marine active product isolated from gonochoric Chinese scallop Chlamys farreri which has recently been found to be an effective antioxidant. In this study, we assessed the effect of PCF on UVB-induced intracellular signalling of apoptosis in HaCaT cells. Pre-treatment with PCF significantly inhibited UVB-induced apoptosis in HaCaT cells. PCF strongly reduced the intracellular reactive oxygen species (ROS) level followed by inhibiting the release of cytochrome c. The expression of CD95 and Fas-associating protein with death domain (FADD) was eliminated in a dose-dependent manner by PCF pre-treatment in UVB-irradiated HaCaT cells, followed by inhibition of cleavage of procaspase-8, whose activation induced cell apoptosis. Furthermore, pre-treatment with the ROS scavenger N-acetylcysteine (NAC) and the caspase-8 inhibitor z-IETD-fmk was found to effectively prevent UVB-induced apoptosis, suggesting that UVB-induced HaCaT cell apoptosis was partially due to generation of ROS and activation of the caspase-8 pathway. Consequently, the protective effect of PCF against UVB irradiation in HaCaT cells is exerted by suppression of generation of ROS followed by inhibition of cytochrome c release and inactivation of Fas-FADD-caspase-8 pathway, resulting in blockage of UVB-induced apoptosis.
栉孔扇贝多肽（PCF）是从雌雄异体的中国栉孔扇贝中分离出的一种新型海洋活性产物，最近被发现是一种有效的抗氧化剂。在本研究中，我们评估了PCF对UVB诱导的HaCaT细胞内凋亡信号传导的影响。PCF预处理可显著抑制UVB诱导的HaCaT细胞凋亡。PCF强烈降低细胞内活性氧（ROS）水平，随后抑制细胞色素c的释放。在UVB照射的HaCaT细胞中，PCF预处理以剂量依赖的方式消除了CD95和死亡结构域相关蛋白Fas（FADD）的表达，随后抑制了procaspase-8的裂解，其激活诱导细胞凋亡。此外，发现用ROS清除剂N-乙酰半胱氨酸（NAC）和caspase-8抑制剂z-IETD-fmk预处理可有效预防UVB诱导的凋亡，这表明UVB诱导的HaCaT细胞凋亡部分归因于ROS的产生和caspase-8途径的激活。因此，PCF对HaCaT细胞UVB照射的保护作用是通过抑制ROS的产生，随后抑制细胞色素c的释放和Fas-FADD-caspase-8途径的失活来实现的，从而导致UVB诱导的凋亡受阻。
