Autophagy induction by SIRT6 is involved in oxidative stress-induced neuronal damage.
Autophagy induction by SIRT6 is involved in oxidative stress-induced neuronal damage.
复制标题
SIRT6 诱导自噬参与氧化应激诱导的神经元损伤
DOI：
10.1007/s13238-016-0257-6
复制
发表时间：
2016-04
期刊：
影响因子：
21.1
通讯作者：
Xia W
中科院分区：
文献类型：
--
作者：
Shao J;Yang X;Liu T;Zhang T;Xie QR;Xia W
SIRT 6是一种NAD+依赖性组蛋白脱乙酰酶，参与基因组稳定性、DNA修复、代谢稳态和多种疾病的调节。SIRT 6在脑缺血和氧/葡萄糖剥夺（OGD）中的作用已被报道，然而SIRT 6在氧化应激损伤中的作用仍不清楚。在这里，我们使用SH-SY 5 Y神经元细胞，发现SIRT 6的过表达导致细胞活力降低，坏死细胞死亡和氧化应激下活性氧（ROS）产生增加。机制研究表明，SIRT 6通过减弱AKT信号转导诱导自噬，自噬抑制剂3-MA或自噬相关蛋白Atg 5的敲低治疗可挽救H2 O2诱导的神经元损伤。相反，SIRT 6抑制抑制自噬并减少氧化应激诱导的神经元损伤。这些结果表明SIRT 6可能是神经保护的潜在治疗靶点。
SIRT6 is a NAD+-dependent histone deacetylase and has been implicated in the regulation of genomic stability, DNA repair, metabolic homeostasis and several diseases. The effect of SIRT6 in cerebral ischemia and oxygen/glucose deprivation (OGD) has been reported, however the role of SIRT6 in oxidative stress damage remains unclear. Here we used SH-SY5Y neuronal cells and found that overexpression of SIRT6 led to decreased cell viability and increased necrotic cell death and reactive oxygen species (ROS) production under oxidative stress. Mechanistic study revealed that SIRT6 induced autophagy via attenuation of AKT signaling and treatment with autophagy inhibitor 3-MA or knockdown of autophagy-related protein Atg5 rescued H2O2-induced neuronal injury. Conversely, SIRT6 inhibition suppressed autophagy and reduced oxidative stress-induced neuronal damage. These results suggest that SIRT6 might be a potential therapeutic target for neuroprotection.