Resveratrol is a class IA phosphoinositide 3-kinase inhibitor

Resveratrol is a class IA phosphoinositide 3-kinase inhibitor
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DOI:
10.1042/bj20070236
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发表时间:
2007-09-15
影响因子:
4.1
通讯作者:
Pirola, Luciano
Pirola, Luciano
中科院分区:
生物学3区
文献类型:
--
作者:
Froejdoe, Sara;Cozzone, Delphine;Pirola, Luciano

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白藜芦醇是一种在水果中发现的多酚,具有化学预防和化学治疗的特性,已被证明可以延长酵母和后生动物(包括小鼠)的寿命。遗传证据和体外酶测量表明,脱乙酰酶Sir 2/SIRT 1,一种促进抗应激和衰老的酶,是白藜芦醇的目标。同样,胰岛素样途径的下调,其中PI 3 K(磷酸肌醇3-激酶)是一个关键的介质,促进长寿,是一个有吸引力的策略,以打击癌症。我们在这里表明,白藜芦醇抑制,在体外和培养的肌肉细胞系,IA类PI 3 K及其下游信号在相同的浓度范围内,它激活sirtuins。我们的观察将IA类PI 3 K定义为白藜芦醇的靶点,其可能有助于促进长寿和抗癌特性,并将白藜芦醇鉴定为天然类特异性PI 3 K抑制剂。
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.