SIRT2通过调节PC12细胞中的Akt磷酸化来介导NADH诱导的Nrf2、GCL和谷胱甘肽增加。
SIRT2 mediates NADH-induced increases in Nrf2, GCL, and glutathione by modulating Akt phosphorylation in PC12 cells.
作者信息
Cao Wei, Hong Yunyi, Chen Heyu, Wu Fan, Wei Xunbin, Ying Weihai
机构信息
Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, China.
School of Naval Architecture, Ocean & Civil Engineering, Shanghai Jiao Tong University, China.
出版信息
FEBS Lett. 2016 Jul;590(14):2241-55. doi: 10.1002/1873-3468.12236. Epub 2016 Jun 17.
SIRT2 plays important roles in multiple biological processes. It is unclear whether SIRT2 affects antioxidant capacity by modulating Nrf2, a key transcription factor for multiple antioxidant genes. By studying NADH-treated differentiated PC12 cells, we found that NADH induced a significant increase in the nuclear Nrf2, which was prevented by both SIRT2 siRNA and SIRT2 inhibitor, AGK2. SIRT2 siRNA also blocked the NADH-induced increases in glutamate cysteine ligase (GCL) and glutathione. Moreover, SIRT2 siRNA and AGK2 blocked NADH-induced Akt phosphorylation, and inhibition of Akt phosphorylation prevented NADH-induced increases in the nuclear Nrf2 and glutathione. Collectively, our study shows that SIRT2 regulates nuclear Nrf2 levels by modulating Akt phosphorylation, thus modulating the levels of GCL and total glutathione.
SIRT2在多个生物学过程中发挥重要作用。目前尚不清楚SIRT2是否通过调节Nrf2（多种抗氧化基因的关键转录因子）来影响抗氧化能力。通过研究经NADH处理的分化PC12细胞，我们发现NADH诱导细胞核内Nrf2显著增加，而SIRT2 siRNA和SIRT2抑制剂AGK2均可阻止这种增加。SIRT2 siRNA还可阻断NADH诱导的谷氨酸半胱氨酸连接酶（GCL）和谷胱甘肽增加。此外，SIRT2 siRNA和AGK2可阻断NADH诱导的Akt磷酸化，抑制Akt磷酸化可阻止NADH诱导的细胞核内Nrf2和谷胱甘肽增加。总体而言，我们的研究表明，SIRT2通过调节Akt磷酸化来调节细胞核内Nrf2水平，从而调节GCL和总谷胱甘肽水平。
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