Fröjdö Sara, Cozzone Delphine, Vidal Hubert, Pirola Luciano
Inserm U-870, INRA U-1235, INSA/UCBL/HCL, Laennec Medical Faculty, Claude Bernard-University Lyon 1, Lyon, France.
Biochem J. 2007 Sep 15;406(3):511-8. doi: 10.1042/BJ20070236.
Resveratrol, a polyphenol found in fruits, possesses chemopreventive and chemotherapeutic properties and has been shown to increase lifespan in yeast and metazoans, including mice. Genetic evidence and in vitro enzymatic measurements indicate that the deacetylase Sir2/SIRT1, an enzyme promoting stress resistance and aging, is the target of resveratrol. Similarly, down-regulation of insulin-like pathways, of which PI3K (phosphoinositide 3-kinase) is a key mediator, promotes longevity and is an attractive strategy to fight cancer. We show here that resveratrol inhibits, in vitro and in cultured muscle cell lines, class IA PI3K and its downstream signalling at the same concentration range at which it activates sirtuins. Our observations define class IA PI3K as a target of resveratrol that may contribute to the longevity-promoting and anticancer properties and identify resveratrol as a natural class-specific PI3K inhibitor.
白藜芦醇是一种存在于水果中的多酚,具有化学预防和化学治疗特性,并且已被证明能延长酵母和后生动物(包括小鼠)的寿命。遗传学证据和体外酶活性测定表明,促进抗应激和衰老的脱乙酰酶Sir2/SIRT1是白藜芦醇的作用靶点。同样,胰岛素样信号通路的下调(PI3K(磷脂酰肌醇3激酶)是该通路的关键介质)可促进长寿,是一种有吸引力的抗癌策略。我们在此表明,在体外和培养的肌肉细胞系中,白藜芦醇在激活去乙酰化酶的相同浓度范围内,可抑制IA类PI3K及其下游信号传导。我们的观察结果将IA类PI3K定义为白藜芦醇的一个靶点,这可能有助于其促进长寿和抗癌特性,并确定白藜芦醇为一种天然的、具有类特异性的PI3K抑制剂。