Kim Hyo Jin, Lee Ki Won, Kim Mi-Sung, Lee Hyong Joo
Department of Agricultural Biotechnology and Center for Agricultural Biomaterials, Seoul National University, Seoul 151-921, Republic of Korea.
J Nutr Biochem. 2008 Jul;19(7):459-66. doi: 10.1016/j.jnutbio.2007.06.001. Epub 2007 Sep 14.
There is mounting evidence implicating the accumulation of intracellular reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the pathogenesis of neurodegenerative disorders, including Alzheimer's disease. Recently, considerable attention has been focused on identifying naturally occurring antioxidants that are able to reduce excess ROS and RNS, thereby protecting against oxidative stress and neuron death. The present study investigated the possible protective effects of piceatannol (trans-3,4,3',5'-tetrahydroxystilbene), which is present in grapes and other foods, on hydrogen-peroxide- and peroxynitrite-induced oxidative cell death. PC12 rat pheochromocytoma (PC12) cells treated with hydrogen peroxide or SIN-1 (a peroxynitrite-generating compound) exhibited apoptotic death, as determined by nucleus condensation and cleavage of poly(ADP-ribose)polymerase (PARP). Piceatannol treatment attenuated hydrogen-peroxide- and peroxynitrite-induced cytotoxicity, apoptotic features, PARP cleavage and intracellular ROS and RNS accumulation. Treatment of PC12 cells with hydrogen peroxide or SIN-1 led to down-regulation of Bcl-X(L) and activation of caspase-3 and -8, which were also inhibited by piceatannol treatment. Hydrogen peroxide or SIN-1 treatment induced phosphorylation of the c-Jun-N-terminal kinase (JNK), which was inhibited by piceatannol treatment. Moreover, SP600125 (a JNK inhibitor) significantly inhibited hydrogen-peroxide- and peroxynitrite-induced PC12 cell death, revealing inactivation of the JNK pathway as a possible molecular mechanism for the protective effects of piceatannol against hydrogen-peroxide- and peroxynitrite-induced apoptosis of PC12 cells. Collectively, these findings suggest that the protective effect of piceatannol against hydrogen-peroxide- and peroxynitrite-induced apoptosis of PC12 cells is associated with blocking the activation of JNK and the down-regulation of Bcl-XL.
越来越多的证据表明，细胞内活性氧（ROS）和活性氮（RNS）的积累与包括阿尔茨海默病在内的神经退行性疾病的发病机制有关。最近，人们将大量注意力集中在寻找能够减少过量ROS和RNS、从而预防氧化应激和神经元死亡的天然抗氧化剂上。本研究调查了葡萄和其他食物中含有的白皮杉醇（反式-3,4,3',5'-四羟基芪）对过氧化氢和过氧亚硝酸根诱导的氧化细胞死亡可能具有的保护作用。用过氧化氢或SIN-1（一种过氧亚硝酸根生成化合物）处理的PC12大鼠嗜铬细胞瘤（PC12）细胞表现出凋亡性死亡，这通过细胞核浓缩和聚（ADP-核糖）聚合酶（PARP）的裂解来确定。白皮杉醇处理减轻了过氧化氢和过氧亚硝酸根诱导的细胞毒性、凋亡特征、PARP裂解以及细胞内ROS和RNS的积累。用过氧化氢或SIN-1处理PC12细胞导致Bcl-X(L)下调以及caspase-3和-8激活，而白皮杉醇处理也抑制了这些变化。过氧化氢或SIN-1处理诱导c-Jun氨基末端激酶（JNK）磷酸化，而白皮杉醇处理抑制了这种磷酸化。此外，SP600125（一种JNK抑制剂）显著抑制了过氧化氢和过氧亚硝酸根诱导的PC12细胞死亡，表明JNK通路失活是白皮杉醇对过氧化氢和过氧亚硝酸根诱导的PC12细胞凋亡具有保护作用的一种可能分子机制。总的来说，这些发现表明白皮杉醇对过氧化氢和过氧亚硝酸根诱导的PC12细胞凋亡的保护作用与阻断JNK激活和Bcl-XL下调有关。
