沉默SIRT2会诱导PC12细胞死亡并降低其细胞内ATP水平。
Silencing of SIRT2 induces cell death and a decrease in the intracellular ATP level of PC12 cells.
作者信息
Nie Hui, Chen Heyu, Han Jin, Hong Yunyi, Ma Yingxin, Xia Weiliang, Ying Weihai
出版信息
Int J Physiol Pathophysiol Pharmacol. 2011;3(1):65-70. Epub 2011 Feb 20.
Abstract
Sirtuin 2 (SIRT2), a tubulin deacetylase, is a sirtuin family protein. SIRT2 inhibitors have been shown to decrease the cell death in cellular and Drosophila models of Parkinson's disease. However, SIRT2 decreases may also compromise cellular antioxidation capacity. Our current study found that silencing of SIRT2 led to a decrease in the intracellular ATP level of PC12 cells. We also found that AGK2, a selective SIRT2 inhibitor, can exacerbate H2O2-induced decreases in the intracellular ATP level of these cells. Our study further indicated that the reduction in SIRT2 level significantly increased necrosis of PC12 cells without affecting autophagy of the cells. These results suggest that SIRT2 is a key mediator of energy metabolism and basal survival of PC12 cells.
摘要
沉默调节蛋白2（SIRT2）是一种微管蛋白脱乙酰酶，属于沉默调节蛋白家族。在帕金森病的细胞模型和果蝇模型中，SIRT2抑制剂已被证明可减少细胞死亡。然而，SIRT2水平降低也可能损害细胞抗氧化能力。我们目前的研究发现，沉默SIRT2会导致PC12细胞内ATP水平降低。我们还发现，选择性SIRT2抑制剂AGK2可加剧H2O2诱导的这些细胞内ATP水平下降。我们的研究进一步表明，SIRT2水平降低显著增加了PC12细胞的坏死，而不影响细胞的自噬。这些结果表明，SIRT2是PC12细胞能量代谢和基础存活的关键调节因子。
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