Wang Sheng-Jun, Zhao Xiu-He, Chen Wen, Bo Ning, Wang Xian-Jin, Chi Zhao-Fu, Wu Wei
Department of Neurology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
Department of Neurology, Jinan Central Hospital, Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China.
Mol Med Rep. 2015 Jan;11(1):521-6. doi: 10.3892/mmr.2014.2724. Epub 2014 Oct 21.
Sirtuin 1 (SIRT1) regulates numerous neuronal processes, including metabolism, antioxidation and aging, through activation of peroxisome proliferator-activated receptor coactivator 1-α (PGC-1α), an upstream regulator of mitochondrial biogenesis and function. However, the role of SIRT1 in the oxidative stress induced by seizures has yet to be elucidated. The present study aimed to investigate whether SIRT1 was involved in the activation of the PGC-1α/mitochondrial antioxidant system following status epilepticus (SE) in rats. The data demonstrated that SIRT1 expression and activity were enhanced in the rat hippocampus following SE. SIRT1 inhibition effectively blocked the SE-associated increase in PGC-1α and mitochondrial antioxidant enzymes, including superoxide dismutase 2 (SOD2) and uncoupling protein 2 (UCP2). Additionally, it was also demonstrated that the activation of SIRT1 enhanced mitochondrial electron transport chain complex I activity and increased ATP content. In conclusion, the present results suggest that SIRT1 activation may alleviate mitochondrial oxidative stress induced by seizures partially via PGC-1α signaling.
沉默调节蛋白1（SIRT1）通过激活过氧化物酶体增殖物激活受体γ共激活因子1α（PGC-1α）来调节多种神经元过程，包括代谢、抗氧化和衰老，PGC-1α是线粒体生物发生和功能的上游调节因子。然而，SIRT1在癫痫发作诱导的氧化应激中的作用尚未阐明。本研究旨在探讨SIRT1是否参与大鼠癫痫持续状态（SE）后PGC-1α/线粒体抗氧化系统的激活。数据表明，SE后大鼠海马中SIRT1的表达和活性增强。SIRT1抑制有效阻断了SE相关的PGC-1α和线粒体抗氧化酶（包括超氧化物歧化酶2（SOD2）和解偶联蛋白2（UCP2））的增加。此外，还证明SIRT1的激活增强了线粒体电子传递链复合体I的活性并增加了ATP含量。总之，目前的结果表明，SIRT1激活可能部分通过PGC-1α信号减轻癫痫发作诱导的线粒体氧化应激。
