Free [NADH]/[NAD+] regulates sirtuin expression
Free [NADH]/[NAD+] regulates sirtuin expression
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DOI：
10.1016/j.abb.2011.04.020
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发表时间：
2011-08-01
影响因子：
3.9
通讯作者：
Vina, Jose
中科院分区：
文献类型：
--
作者：
Gambini, Juan;Carmen Gomez-Cabrera, Mari;Vina, Jose
Sirtuins 是参与代谢调节和长寿的脱乙酰酶。我们的目的是检验它们受到 [NADH]/[NAD(+)] 比率氧化还原调节的假设。我们在培养中使用了 NIH3T3 成纤维细胞，用或不用乙醇喂养的果蝇以及锻炼的大鼠。在所有三种模型中，[NADH]/[NAD(+)] 的增加都会导致沉默调节蛋白 mRNA 和蛋白质表达的增加。在与乳酸和丙酮酸一起孵育的成纤维细胞中，PGC-1 α（sirtuins 的底物）蛋白水平显着增加，但这种效果在从 Sirtuin 缺陷小鼠获得的成纤维细胞中消失。我们得出结论，sirtuins 的表达受到 [NADH]/[NAD(+)] 比率的严格氧化还原调节，这是从无脊椎动物到脊椎动物保守的代谢物可用性的主要传感器。 (c) 2011 年，爱思唯尔公司出版。
Sirtuins are deacetylases involved in metabolic regulation and longevity. Our aim was to test the hypothesis that they are subjected to redox regulation by the [NADH]/[NAD(+)] ratio. We used NIH3T3 fibroblasts in culture, Drosophila fed with or without ethanol and exercising rats. In all three models an increase in [NADH]/[NAD(+)] came up with an increased expression of sirtuin mRNA and protein. PGC-1 alpha (a substrate of sirtuins) protein level was significantly increased in fibroblasts incubated with lactate and pyruvate but this effect was lost in fibroblasts obtained from sirtuin-deficient mice.We conclude that the expression of sirtuins is subject to tight redox regulation by the [NADH]/[NAD(+)] ratio, which is a major sensor for metabolite availability conserved from invertebrates to vertebrates. (c) 2011 Published by Elsevier Inc.