Medical Sciences Division, Northern Ontario School of Medicine, Sudbury, ON, Canada.
Biochem Biophys Res Commun. 2010 Mar 19;393(4):773-8. doi: 10.1016/j.bbrc.2010.02.079. Epub 2010 Feb 18.
Neurodegenerative disorders are a class of diseases that have been linked to apoptosis induced by elevated levels of reactive oxygen species (ROS). ROS activates the apoptotic cascade through mitochondrial dysfunction and damage to lipids, proteins and DNA. Recently, fruit and tea-derived polyphenols have been found to be beneficial in decreasing oxidative stress and increasing overall health. Further, polyphenols including epigallocatechin gallate (EGCG) have been reported to inhibit apoptotic signaling and increase neural cell survival. In an effort to better understand the beneficial properties associated with polyphenol consumption, the aim of this study was to explore the neuroprotective effects of EGCG, methyl gallate (MG), gallic acid (GA) and N-acetylcysteine (NAC) on H(2)O(2)-induced apoptosis in PC12 cells and elucidate potential protective mechanisms. Cell viability data demonstrates that MG and NAC pre-treatments significantly increase viability of H(2)O(2)-stressed cells, while pre-treatments with EGCG and GA exacerbates stress. Quantitation of apoptosis and mitochondrial membrane potential shows that MG pre-treatment prevents mitochondria depolarization, however does not inhibit apoptosis and is thus evidence that MG can inhibit mitochondria-mediated apoptosis. Subsequent analysis of DNA degradation and caspase activation reveals that MG inhibits activation of caspase 9 and has a partial inhibitory effect on DNA degradation. These findings confirm the involvement of both intrinsic and extrinsic apoptotic pathways in H(2)O(2)-induced apoptosis and suggest that MG may have potential therapeutic properties against mitochondria-mediated apoptosis.
神经退行性疾病是一类与活性氧（ROS）水平升高诱导的细胞凋亡有关的疾病。ROS 通过线粒体功能障碍和脂质、蛋白质和 DNA 的损伤激活凋亡级联。最近，发现水果和茶来源的多酚类物质有益于减少氧化应激和提高整体健康水平。此外，有报道称，包括表没食子儿茶素没食子酸酯（EGCG）在内的多酚类物质可以抑制细胞凋亡信号通路并增加神经细胞的存活率。为了更好地了解与多酚类物质消耗相关的有益特性，本研究旨在探讨 EGCG、甲基没食子酸酯（MG）、没食子酸（GA）和 N-乙酰半胱氨酸（NAC）对 PC12 细胞中 H2O2 诱导的细胞凋亡的神经保护作用，并阐明潜在的保护机制。细胞活力数据表明，MG 和 NAC 的预处理显著增加了 H2O2 应激细胞的活力，而 EGCG 和 GA 的预处理则加剧了应激。凋亡和线粒体膜电位的定量表明，MG 预处理可防止线粒体去极化，但不能抑制凋亡，这表明 MG 可以抑制线粒体介导的凋亡。随后对 DNA 降解和半胱天冬酶激活的分析表明，MG 抑制了 caspase-9 的激活，并对 DNA 降解有部分抑制作用。这些发现证实了 H2O2 诱导的细胞凋亡涉及内在和外在的凋亡途径，并表明 MG 可能具有针对线粒体介导的细胞凋亡的潜在治疗特性。
