Laboratório de Química de Produtos Naturais, Departamento de Química Pura, Faculdade de Química, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681 Porto Alegre, RS 90619-900, Brazil.
Mol Biol Rep. 2012 Mar;39(3):3281-9. doi: 10.1007/s11033-011-1096-4. Epub 2011 Jun 25.
Sirtuins (SIRTs) are NAD(+)-dependent deacetylases that catalyze the hydrolysis of acetyl-lysine residues. They play an important role in many physiological and pathophysiological processes, such as the regulation of lifespan and the prevention of metabolic diseases. In this study, we analyzed the effect of resveratrol on the gene expression levels of SIRT1, SIRT3, SIRT4, PGC1α, and NAMPT, as well as its effect on NAD(+) and NADH levels, in the liver of non stressed or non impaired wild-type zebrafish. Semiquantative RT-PCR assays showed that resveratrol did not change the mRNA levels of SIRT1 and PGC1α but decreased the expression levels of the SIRT3, SIRT4, and NAMPT genes. The decrease in NAMPT mRNA levels was accompanied by an increase in NADH levels, thereby decreasing the NAD(+)/H ratio. Taken together, our results suggest that resveratrol plays a modulatory role in the transcription of the NAMPT, SIRT3, and SIRT4 genes. Zebrafish is an interesting tool that can be used to understand the mechanisms of SIRTs and NAMPT metabolism and to help develop therapeutic compounds. However, further investigations using healthy experimental animals are required to study the modulation of the SIRT and NAMPT genes by resveratrol before it is used as a nutraceutical compound in healthy humans.
Sirtuins（SIRTs）是 NAD（+）依赖性去乙酰化酶，可催化乙酰-赖氨酸残基的水解。它们在许多生理和病理生理过程中发挥着重要作用，如寿命的调节和代谢性疾病的预防。在这项研究中，我们分析了白藜芦醇对非应激或非损伤野生型斑马鱼肝脏中 SIRT1、SIRT3、SIRT4、PGC1α 和 NAMPT 基因表达水平的影响，以及对 NAD（+）和 NADH 水平的影响。半定量 RT-PCR 检测表明，白藜芦醇并未改变 SIRT1 和 PGC1α 的 mRNA 水平，但降低了 SIRT3、SIRT4 和 NAMPT 基因的表达水平。NAMPT mRNA 水平的降低伴随着 NADH 水平的增加，从而降低了 NAD（+）/H 比值。总之，我们的结果表明，白藜芦醇在 NAMPT、SIRT3 和 SIRT4 基因的转录中发挥调节作用。斑马鱼是一种有趣的工具，可以用来理解 SIRTs 和 NAMPT 代谢的机制，并有助于开发治疗性化合物。然而，在将白藜芦醇作为健康人类的营养补充剂使用之前，需要使用健康实验动物进行进一步研究，以研究白藜芦醇对 SIRT 和 NAMPT 基因的调节作用。
