Sirtuin 5 is Anti-apoptotic and Anti-oxidative in Cultured SH-EP Neuroblastoma Cells
Sirtuin 5 is Anti-apoptotic and Anti-oxidative in Cultured SH-EP Neuroblastoma Cells
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DOI：
10.1007/s12640-016-9664-y
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发表时间：
2017-01-01
影响因子：
3.7
通讯作者：
Ong, Wei Chen
中科院分区：
文献类型：
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作者：
Liang, Fengyi;Wang, Xie;Ong, Wei Chen
sirtuin 5 （SIRT5）是一种烟酰胺腺嘌呤二核苷酸（NAD(+)）依赖的去乙酰化酶、去丙烯化酶和去琥珀酰化酶，据报道，SIRT5存在于宿主细胞的线粒体、细胞质或细胞核中。SIRT5在细胞代谢、能量产生、解毒、氧化应激和凋亡中的各种功能作用也被描述，但一些报道的结果似乎不一致甚至相互矛盾。利用免疫细胞化学、分子生物学、基因转染和流式细胞术等方法，研究了SIRT5在SH-EP神经母细胞瘤细胞中的表达、亚细胞分布以及可能在调节细胞凋亡和氧化应激中的功能作用。在宿主SH-EP细胞的线粒体中均观察到内源性和转染的外源性SIRT5。SIRT5过表达可显著保护SH-EP细胞免受staurosporine或Hank's平衡盐溶液培养诱导的凋亡。SIRT5还能降低氧化应激水平，对抗过氧化氢对SH-EP细胞的毒性。这表明SIRT5的抗凋亡作用至少部分是通过其在SH-EP神经母细胞瘤细胞中的抗氧化作用介导的，尽管其涉及的分子机制仍有待详细阐明。
As a nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase, demalonylase, and desuccinylase, sirtuin 5 (SIRT5) in host cells has been reportedly observed in the mitochondria, in the cytosol/cytoplasm or in the nucleus. Various functional roles of SIRT5 have also been described in cellular metabolism, energy production, detoxification, oxidative stress, and apoptosis, but some of the reported results are seemingly inconsistent or even contradictory to one another. Using immunocytochemistry, molecular biology, gene transfection, and flow cytometry, we investigated the expression, subcellular distribution, and possible functional roles of SIRT5 in regulating apoptosis and oxidative stress of cultured SH-EP neuroblastoma cells. Both endogenous and transfected exogenous SIRT5 were observed in mitochondria of host SH-EP cells. Overexpression of SIRT5 markedly protected SH-EP cells from apoptosis induced by staurosporine or by incubation in Hank's balanced salt solution. SIRT5 also lowered the level of oxidative stress and countered the toxicity of hydrogen peroxide to SH-EP cells. It was suggested that the anti-apoptotic role of SIRT5 was mediated, at least in part, by its anti-oxidative effect in SH-EP neuroblastoma cells although the involved molecular mechanisms remain to be elucidated in details.