Department of Physiology, Faculty of Medicine, University of Valencia, Fundacion Investigacion Hospital Clinico Universitario INCLIVA, Spain.
Arch Biochem Biophys. 2011 Aug 1;512(1):24-9. doi: 10.1016/j.abb.2011.04.020. Epub 2011 May 7.
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-1α (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.
Sirtuins 是参与代谢调节和长寿的去乙酰化酶。我们的目的是验证它们是否受到 [NADH]/[NAD(+)] 比例的氧化还原调节。我们使用培养的 NIH3T3 成纤维细胞、用或不用乙醇喂养的果蝇和运动大鼠进行实验。在所有三种模型中，[NADH]/[NAD(+)] 的增加伴随着沉默信息调节因子 2 相关酶 1（sirtuin 1）mRNA 和蛋白质表达的增加。在与乳酸盐和丙酮酸孵育的成纤维细胞中，PGC-1α（沉默信息调节因子 2 相关酶 1 的底物）蛋白水平显著增加，但这种作用在沉默信息调节因子 2 相关酶 1 缺陷小鼠获得的成纤维细胞中消失。我们得出结论，沉默信息调节因子 2 相关酶 1 的表达受到 [NADH]/[NAD(+)] 比例的严格氧化还原调节，这是一种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。
