Kang Min Kyung, Kang Nam Joo, Jang Young Jin, Lee Ki Won, Lee Hyong Joo
Department of Agricultural Biotechnology, Seoul National University, Seoul, Korea.
Ann N Y Acad Sci. 2009 Aug;1171:514-20. doi: 10.1111/j.1749-6632.2009.04728.x.
Oxidative stress induced by reactive oxygen species (ROS) is strongly associated with the pathogenesis of various neurodegenerative disorders, including Alzheimer's disease. We investigated the possible combined effects of gallic acid and resveratrol, which are major antioxidants present in fruit, including grapes, on PC12 rat pheochromocytoma (PC12) cell death. Gallic acid did not protect against H(2)O(2)-induced PC12 cell death; it reduced the viability of PC12 cells in a dose-dependent manner. Gallic acid also induced cleavage of poly (ADP-ribose) polymerase, which is strongly related to apoptosis in neurons. Gallic acid induced the phosphorylation of c-Jun N-terminal protein kinase (JNK) and the downregulation of Bcl-2 in PC12 cells. Treatment of PC12 cells with resveratrol increased their viability in a dose-dependent manner by blocking the activation of JNK and the downregulation of Bcl-2. Furthermore, gallic acid led to a progressive reduction in the viability of vector-transfected PC12 cells, which was delayed in PC12 cells that overexpressed Bcl-2. The JNK inhibitor SP600125 protected against gallic acid-induced PC12 cell death. Collectively, these findings suggest that the combined effects of dietary phenolic phytochemicals on oxidative neuronal cell death and antioxidants differ in ROS-mediated neuronal cell death.
活性氧（ROS）诱导的氧化应激与包括阿尔茨海默病在内的各种神经退行性疾病的发病机制密切相关。我们研究了水果（包括葡萄）中主要的抗氧化剂没食子酸和白藜芦醇对PC12大鼠嗜铬细胞瘤（PC12）细胞死亡可能的联合作用。没食子酸不能保护PC12细胞免受H₂O₂诱导的细胞死亡；它以剂量依赖的方式降低PC12细胞的活力。没食子酸还诱导聚（ADP - 核糖）聚合酶的裂解，这与神经元凋亡密切相关。没食子酸诱导PC12细胞中c - Jun氨基末端蛋白激酶（JNK）的磷酸化和Bcl - 2的下调。用白藜芦醇处理PC12细胞通过阻断JNK的激活和Bcl - 2的下调以剂量依赖的方式增加其活力。此外，没食子酸导致载体转染的PC12细胞活力逐渐降低，而在过表达Bcl - 2的PC12细胞中这种降低被延迟。JNK抑制剂SP600125可保护PC12细胞免受没食子酸诱导的细胞死亡。总的来说，这些发现表明饮食中的酚类植物化学物质对氧化神经元细胞死亡的联合作用以及抗氧化剂在ROS介导的神经元细胞死亡中存在差异。
