SIRT1 activating compounds reduce oxidative stress and prevent cell death in neuronal cells.
SIRT1 activating compounds reduce oxidative stress and prevent cell death in neuronal cells.
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DOI：
10.3389/fncel.2012.00063
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发表时间：
2012
影响因子：
5.3
通讯作者：
Shindler KS
中科院分区：
文献类型：
--
作者：
Khan RS;Fonseca-Kelly Z;Callinan C;Zuo L;Sachdeva MM;Shindler KS
SIRT1（一种NAD+依赖的去乙酰化酶）的激活可以防止视神经炎（一种炎症性脱髓鞘性视神经疾病）中视网膜神经节细胞（RGC）的损失。虽然SIRT1使许多蛋白靶点去乙酰化，但SIRT1激活介导这种神经保护作用的下游机制尚不清楚。SIRT1增加线粒体功能，减少肌肉和其他细胞的氧化应激，氧化应激发生在神经元变性中。我们研究了SIRT1激活剂是否能降低氧化应激并促进神经元细胞的线粒体功能。血清剥夺、多柔比星或过氧化氢均可诱导RGC-5细胞产生以活性氧（ROS）积累为标志的氧化应激，导致细胞显著损失。SIRT1激活剂resveratrol （RSV）和SRTAW04降低了RGC-5细胞和原代RGC培养物中的ROS水平，并促进了细胞存活。效应被SIRT1 siRNA阻断。SIRT1激活剂还增加了琥珀酸脱氢酶（SDH）的表达，这是一种线粒体酶，并促进PGC-1α的去乙酰化，PGC-1α是一种参与线粒体功能的辅酶。结果表明SIRT1激活剂通过减少氧化应激和促进神经元细胞系的线粒体功能来防止细胞损失。结果表明SIRT1激活剂可以通过这些机制介导视神经炎期间的神经保护作用，并且它们具有保护其他涉及氧化应激的神经退行性疾病中的神经元的潜力。
Activation of SIRT1, an NAD+-dependent deacetylase, prevents retinal ganglion cell (RGC) loss in optic neuritis, an inflammatory demyelinating optic nerve disease. While SIRT1 deacetylates numerous protein targets, downstream mechanisms of SIRT1 activation mediating this neuroprotective effect are unknown. SIRT1 increases mitochondrial function and reduces oxidative stress in muscle and other cells, and oxidative stress occurs in neuronal degeneration. We examined whether SIRT1 activators reduce oxidative stress and promote mitochondrial function in neuronal cells. Oxidative stress, marked by reactive oxygen species (ROS) accumulation, was induced in RGC-5 cells by serum deprivation, or addition of doxorubicin or hydrogen peroxide, and resulted in significant cell loss. SIRT1 activators resveratrol (RSV) and SRTAW04 reduced ROS levels and promoted cell survival in RGC-5 cells as well as primary RGC cultures. Effects were blocked by SIRT1 siRNA. SIRT1 activators also increased expression of succinate dehydrogenase (SDH), a mitochondrial enzyme, and promoted deacetylation of PGC-1α, a co-enzyme involved in mitochondrial function. Results show SIRT1 activators prevent cell loss by reducing oxidative stress and promoting mitochondrial function in a neuronal cell line. Results suggest SIRT1 activators can mediate neuroprotective effects during optic neuritis by these mechanisms, and they have the potential to preserve neurons in other neurodegenerative diseases that involve oxidative stress.
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影响因子：
3.4
作者：
Fonseca-Kelly Z;Nassrallah M;Uribe J;Khan RS;Dine K;Dutt M;Shindler KS
通讯作者：
Shindler KS
DOI：
10.1016/j.bbapap.2009.10.025
发表时间：
2010-08
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Baur JA
通讯作者：
Baur JA
影响因子：
3.3
作者：
Cowden, WB;Cullen, FA;Willenborg, DO
通讯作者：
Willenborg, DO
DOI：
10.1196/annals.1353.024
发表时间：
2006-01-01
期刊：
PHEOCHROMOCYTOMA
影响因子：
--
作者：
Baysal, Bora E.
通讯作者：
Baysal, Bora E.
MOG 特异性 TCR 转基因小鼠自发性自身免疫性视神经炎引起的视网膜神经节细胞损伤
影响因子：
3.3
作者：
Guan, Yangtai;Shindler, Kenneth S.;Rostami, A. M.
通讯作者：
Rostami, A. M.