Sirt3 protects cortical neurons against oxidative stress via regulating mitochondrial Ca2+ and mitochondrial biogenesis.
Sirt3 protects cortical neurons against oxidative stress via regulating mitochondrial Ca2+ and mitochondrial biogenesis.
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Sirt3 通过调节线粒体 Ca2 和线粒体生物发生来保护皮质神经元免受氧化应激
DOI：
10.3390/ijms150814591
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发表时间：
2014-08-21
影响因子：
5.6
通讯作者：
Jiang XF
中科院分区：
文献类型：
--
作者：
Dai SH;Chen T;Wang YH;Zhu J;Luo P;Rao W;Yang YF;Fei Z;Jiang XF
氧化应激是几种神经生物学疾病的病理学中公认的事件。Sirt3是烟酰胺腺嘌呤核苷酸（NAD+）依赖性蛋白脱乙酰酶，其响应于热量限制和应激而调节线粒体功能和代谢。本研究旨在探讨Sirt3在H2O2诱导的原代培养大鼠皮层神经元氧化损伤中的作用。我们发现，H2O2处理显着增加Sirt3的表达在mRNA和蛋白水平上的时间依赖性的方式。用特异性小干扰RNA（siRNA）敲低Sirt3可加重H2O2诱导的神经元损伤，而慢病毒转染过表达Sirt3可抑制H2O2诱导的神经元损伤，减少活性氧（ROS）的产生，并增加内源性抗氧化酶的活性。此外，线粒体内的Ca2+超载，但不是胞浆Ca2+增加H2O2处理后，强烈减弱后Sirt3过表达。Sirt3的过表达还增加了线粒体DNA（mtDNA）的含量和线粒体生物合成相关转录因子的表达。所有这些结果表明，Sirt3作为一个促生存因子发挥重要作用，以保护皮质神经元在H2O2诱导的氧化应激，可能通过调节线粒体Ca 2+稳态和线粒体生物合成。
Oxidative stress is a well-established event in the pathology of several neurobiological diseases. Sirt3 is a nicotinamide adenine nucleotide (NAD+)-dependent protein deacetylase that regulates mitochondrial function and metabolism in response to caloric restriction and stress. This study aims to investigate the role of Sirt3 in H2O2 induced oxidative neuronal injury in primary cultured rat cortical neurons. We found that H2O2 treatment significantly increased the expression of Sirt3 in a time-dependent manner at both mRNA and protein levels. Knockdown of Sirt3 with a specific small interfering RNA (siRNA) exacerbated H2O2-induced neuronal injury, whereas overexpression of Sirt3 by lentivirus transfection inhibited H2O2-induced neuronal damage reduced the generation of reactive oxygen species (ROS), and increased the activities of endogenous antioxidant enzymes. In addition, the intra-mitochondrial Ca2+ overload, but not cytosolic Ca2+ increase after H2O2 treatment, was strongly attenuated after Sirt3 overexpression. Overexpression of Sirt3 also increased the content of mitochondrial DNA (mtDNA) and the expression of mitochondrial biogenesis related transcription factors. All these results suggest that Sirt3 acts as a prosurvival factor playing an essential role to protect cortical neurons under H2O2 induced oxidative stress, possibly through regulating mitochondrial Ca2+ homeostasis and mitochondrial biogenesis.
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