School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, PR China.
Neurosci Lett. 2013 Jun 7;544:36-40. doi: 10.1016/j.neulet.2013.03.032. Epub 2013 Apr 6.
Sirtuin 2 (SIRT2), a sirtuin family protein, is a tubulin deacetylase. Recent studies have indicated that SIRT2 plays a key role in programmed necrosis, and the SIRT2 inhibitor AGK2 can decrease the cell death both in a cellular model of Parkinson's disease and in an animal model of myocardial ischemia-reperfusion. However, there has been little information regarding the role of SIRT2 in microglial survival and functions, which play critical roles in multiple neurological disorders. Our current study found that AGK2 at 10 μM - a widely used AGK2 concentration - can induce both late-stage apoptosis and necrosis, as well as a decrease in the intracellular ATP levels of microglial BV2 cells. Our study also showed that both the AGK2-induced cell death and the AGK2-induced ATP decline are mediated by poly(ADP-ribose) polymerase (PARP) activation. Collectively, our study has provided the first evidence suggesting a significant role of SIRT2 in the basal survival of microglia, as well as a mechanism accounting for the effects of SIRT2 on intracellular ATP levels.
Sirtuin 2（SIRT2）是一种组蛋白去乙酰化酶，属于 sirtuin 家族蛋白。最近的研究表明 SIRT2 在编程性细胞坏死中发挥关键作用，SIRT2 抑制剂 AGK2 可减少帕金森病细胞模型和心肌缺血再灌注动物模型中的细胞死亡。然而，关于 SIRT2 在小胶质细胞存活和功能中的作用的信息很少，小胶质细胞在多种神经疾病中发挥着关键作用。我们目前的研究发现，10μM 的 AGK2（一种广泛使用的 AGK2 浓度）可诱导小胶质细胞 BV2 细胞晚期凋亡和坏死，并降低细胞内 ATP 水平。我们的研究还表明，AGK2 诱导的细胞死亡和 AGK2 诱导的 ATP 下降均由聚（ADP-核糖）聚合酶（PARP）激活介导。总之，我们的研究首次提供了证据表明 SIRT2 在小胶质细胞基础存活中发挥重要作用，并阐明了 SIRT2 对细胞内 ATP 水平的影响的机制。
