博文
白藜芦醇激活SIRT1作用机理揭秘
|||
【文献导读】
今年2月，Cell杂志发表了美、中、荷科学家共同完成的揭示白藜芦醇激活SIRT1作用机理的研究论文（非开放获取）。从文章题目和摘要可知，白藜芦醇的作用靶点是环腺苷酸（cAMP）磷酸二酯酶（PDE），其级联途径见下图：
首先，白藜芦醇抑制PDE活性，导致cAMP降解减少，促进Epac1活化，使Ca2+从内质网释放，激活CamKKβ和AMPK，提高PGC1ɑ和SIRT1活性，使骨骼肌中的线粒体功能增强。有趣的是，抗精神病药物洛利普兰居然能模拟白藜芦醇的作用，真是令人诧异！
该文题目及摘要如下：
Resveratrol Ameliorates Aging-Related Metabolic Phenotypes by Inhibiting cAMP Phosphodiesterases
Resveratrol, a polyphenol in red wine, has been reported as a calorie restriction mimetic with potential antiaging and antidiabetogenic properties. It is widely consumed as a nutritional supplement, but its mechanism of action remains a mystery. Here, we report that the metabolic effects of resveratrol result from competitive inhibition of cAMP-degrading phosphodiesterases, leading to elevated cAMP levels. The resulting activation of Epac1, a cAMP effector protein, increases intracellular Ca2+ levels and activates the CamKKβ-AMPK pathway via phospholipase C and the ryanodine receptor Ca2+-release channel. As a consequence, resveratrol increases NAD+ and the activity of Sirt1. Inhibiting PDE4 with rolipram reproduces all of the metabolic benefits of resveratrol, including prevention of diet-induced obesity and an increase in mitochondrial function, physical stamina, and glucose tolerance in mice. Therefore, administration of PDE4 inhibitors may also protect against and ameliorate the symptoms of metabolic diseases associated with aging.
https://blog.sciencenet.cn/blog-281238-582466.html
上一篇：雷帕霉素：“鱼和熊掌不能兼得”的长寿药
下一篇：如何让科普文章更好看
