Sirtuins and renal diseases: relationship with aging and diabetic nephropathy.
Sirtuins and renal diseases: relationship with aging and diabetic nephropathy.
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DOI：
10.1042/cs20120190
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发表时间：
2013-02
期刊：
影响因子：
--
通讯作者：
Koya D
中科院分区：
文献类型：
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作者：
Kitada M;Kume S;Takeda-Watanabe A;Kanasaki K;Koya D
Sirtuins是Sir 2（沉默信息调节因子2）家族的成员，该家族是一组III类脱乙酰酶。哺乳动物有七种不同的sirtuins，SIRT 1-SIRT 7。其中，SIRT 1、SIRT 3和SIRT 6是由热量限制条件诱导的，被认为是抗衰老分子。SIRT 1是研究最广泛的。SIRT 1使用辅酶NAD+使靶蛋白脱乙酰基，因此通过多种信号传导和存活途径与细胞能量代谢和氧化还原状态相关。在各种应激条件下，如代谢或氧化应激或缺氧，SIRT 1缺陷涉及年龄相关疾病的病理生理学，包括糖尿病，心血管疾病，神经退行性疾病和肾脏疾病。在肾脏中，SIRT 1可以抑制肾细胞凋亡、炎症和纤维化，并且可以调节脂质代谢、自噬、血压和钠平衡。因此，肾脏中SIRT 1的激活可能是一个新的治疗靶点，以增加对肾脏疾病（包括糖尿病肾病）发展中许多致病因素的抵抗力。此外，SIRT 3和SIRT 6与年龄相关的疾病或寿命有关。在本综述中，我们讨论了sirtuins的保护功能和sirtuins与肾脏疾病，包括糖尿病肾病的病理生理学的关联。
Sirtuins are members of the Sir2 (silent information regulator 2) family, a group of class III deacetylases. Mammals have seven different sirtuins, SIRT1–SIRT7. Among them, SIRT1, SIRT3 and SIRT6 are induced by calorie restriction conditions and are considered anti-aging molecules. SIRT1 has been the most extensively studied. SIRT1 deacetylates target proteins using the coenzyme NAD+ and is therefore linked to cellular energy metabolism and the redox state through multiple signalling and survival pathways. SIRT1 deficiency under various stress conditions, such as metabolic or oxidative stress or hypoxia, is implicated in the pathophysiologies of age-related diseases including diabetes, cardiovascular diseases, neurodegenerative disorders and renal diseases. In the kidneys, SIRT1 may inhibit renal cell apoptosis, inflammation and fibrosis, and may regulate lipid metabolism, autophagy, blood pressure and sodium balance. Therefore the activation of SIRT1 in the kidney may be a new therapeutic target to increase resistance to many causal factors in the development of renal diseases, including diabetic nephropathy. In addition, SIRT3 and SIRT6 are implicated in age-related disorders or longevity. In the present review, we discuss the protective functions of sirtuins and the association of sirtuins with the pathophysiology of renal diseases, including diabetic nephropathy.