Protective Effects of Asiatic Acid on Rotenone- or H2O2-Induced Injury in SH-SY5Y Cells
Protective Effects of Asiatic Acid on Rotenone- or H2O2-Induced Injury in SH-SY5Y Cells
复制标题
DOI：
10.1007/s11064-008-9844-0
复制
发表时间：
2009-04-01
影响因子：
4.4
通讯作者：
Gao, Jing
中科院分区：
文献类型：
--
作者：
Xiong, Yuyun;Ding, Hongqun;Gao, Jing
帕金森病（PD）是一种进行性神经退行性疾病，在50岁以上的人群中的患病率为1-2%。线粒体功能障碍发生在PD患者中，显示复合物I的活性损失15-30%。积雪草酸（AA）是一种三萜类化合物，是一种抗氧化剂，用于治疗抑郁症，但AA对PD样损伤的作用尚未见报道。在本研究中，我们研究了AA对H2 O2或鱼藤酮诱导的SH-SY 5 Y细胞损伤和线粒体功能障碍的保护作用。观察AA预处理对线粒体膜电位（MMP）和电压依赖性阴离子通道（VDAC）表达的影响，探讨AA神经保护作用的可能机制。结果表明，AA（0.01-100 nM）预处理保护细胞免受鱼藤酮或H2 O2诱导的毒性。此外，MMP耗散发生在暴露于鱼藤酮后，这可以通过AA处理来防止。更有趣的是，预先给予AA抑制了由鱼藤酮（100 nM）或H2 O2（300 μ M）诱导的VDAC mRNA和蛋白水平的升高。这些数据表明，AA可以保护神经元细胞免受线粒体功能障碍性损伤，并表明AA可能被开发为PD预防或治疗的药物。
Parkinson's disease (PD) is a progressive neurodegenerative disorder with a prevalence of 1-2% in people over the age of 50. Mitochondrial dysfunction occurred in PD patients showing a 15-30% loss of activity in complex I. Asiatic acid (AA), a triterpenoid, is an antioxidant and used for depression treatment, but the effect of AA against PD-like damage has never been reported. In the present study, we investigated the protective effects of AA against H2O2 or rotenone-induced cellular injury and mitochondrial dysfunction in SH-SY5Y cells. Mitochondrial membrane potential (MMP) and the expression of voltage-dependent anion channel (VDAC) were detected with or without AA pretreatment following cellular injury to address the possible mechanisms of AA neuroprotection. The results showed that pre-treatment of AA (0.01-100 nM) protected cells against the toxicity induced by rotenone or H2O2. In addition, MMP dissipation occurred following the exposure of rotenone, which could be prevented by AA treatment. More interestingly, pre-administration of AA inhibited the elevation of VDAC mRNA and protein levels induced by rotenone(100 nM) or H2O2 (300 mu M).These data indicate that AA could protect neuronal cells against mitochondrial dysfunctional injury and suggest that AA might be developed as an agent for PD prevention or therapy.