Sirtuin regulation in aging and injury.
Sirtuin regulation in aging and injury.
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DOI：
10.1016/j.bbadis.2015.08.017
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发表时间：
2015-11
期刊：
影响因子：
--
通讯作者：
Raju R
中科院分区：
文献类型：
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作者：
Poulose N;Raju R
Sirtuins 或 Sir2 蛋白家族是一类 NAD+ 依赖性蛋白脱乙酰酶，从细菌到人类在进化上都是保守的。一些去乙酰化酶还表现出单 ADP 核糖基转移酶、脱丙二酰化和脱琥珀酰化活性。这些蛋白质最初是在酵母中发现的，它们调节关键的细胞过程，如细胞周期、细胞凋亡、代谢调节和炎症。人类编码七种沉默调节蛋白亚型 SIRT1-SIRT7，具有不同的细胞内分布。除了作为组蛋白脱乙酰酶调节转录的经典作用外，sirtuins 的许多细胞质和线粒体靶标也已被鉴定。 Sirtuins 与长寿有关，越来越多的证据表明它们在癌症、糖尿病、肥胖和神经退行性疾病等一系列疾病中的作用。许多研究报告了 SIRT1 表达和活性的深刻变化，这些变化与缺氧缺血条件和复氧损伤后线粒体功能的改变有关。 SIRT1 介导的 PGC-1α、FOXO3、p53 和 NF-κb 等靶标的脱乙酰化对线粒体功能、细胞凋亡和炎症具有深远影响。这些生物过程和功能对于损伤后的寿命决定和结果至关重要。据报道，衰老的特点是 SIRT1 活性下降，而其表达或激活的增加表明低等动物的寿命延长。 NAD+ 下降导致的假性缺氧状态也与衰老有关。在这篇综述中，我们概述了沉默调节蛋白在衰老和损伤中的作用的研究。
Sirtuins or Sir2 family of proteins are a class of NAD+ dependent protein deacetylases which are evolutionarily conserved from bacteria to humans. Some sirtuins also exhibit mono-ADP ribosyl transferase, demalonylation and desuccinylation activities. Originally identified in the yeast, these proteins regulate key cellular processes like cell cycle, apoptosis, metabolic regulation and inflammation. Humans encode seven sirtuin isoforms SIRT1-SIRT7 with varying intracellular distribution. Apart from their classic role as histone deacetylases regulating transcription, a number of cytoplasmic and mitochondrial targets of sirtuins have also been identified. Sirtuins have been implicated in longevity and accumulating evidences indicate their role in a spectrum of diseases like cancer, diabetes, obesity and neurodegenerative diseases. A number of studies have reported profound changes in SIRT1 expression and activity linked to mitochondrial functional alterations following hypoxic-ischemic conditions and following reoxygenation injury. The SIRT1 mediated deacetylation of targets such as PGC-1α, FOXO3, p53 and NF-κb has profound effect on mitochondrial function, apoptosis and inflammation. These biological processes and functions are critical in life-span determination and outcome following injury. Aging is reported to be characterized by declining SIRT1 activity and its increased expression or activation demonstrated prolonged life-span in lower forms of animals. A pseudohypoxic state due to declining NAD+ has also been implicated in aging. In this review we provide an overview of studies on the role of sirtuins in aging and injury.