摘要/Abstract

摘要： 骨质疏松是一种以骨矿物含量下降、骨微细结构破坏为特征的骨骼疾病，其发病机制与骨骼系统衰老和能量代谢紊乱有关。沉默交配型信息调节因子2同源蛋白1（silent mating-type information regulator 2 homolog 1，SIRT1）是一类烟酰胺腺嘌呤二核苷酸（nicotinamide adenine dinucleotide，NAD+）依赖的去乙酰化酶，是生物体内细胞衰老、能量代谢和骨骼重塑3个重要生理过程的汇合点。SIRT1不仅能被单磷酸腺苷活化蛋白激酶[adenosine 5-monophosphate (AMP)-activated protein kinase，AMPK]、c-Jun氨基末端激酶1（c-Jun N-terminal kinase 1，JNK1）和酪蛋白激酶2（casein kinase 2，CK2）等激酶激活，还能被白藜芦醇等小分子药物激活。这些激酶与药物均能影响骨代谢。且研究证实SIRT1信号通路也能直接调控骨代谢过程，但其中的具体调节机制尚不明确。该文就SIRT1的结构、功能和在骨代谢各个环节中的作用作一综述，并分析SIRT1信号通路作为骨质疏松治疗新靶点的潜力。
关键词: 沉默交配型信息调节因子2同源蛋白1, 去乙酰化, 骨代谢, 骨质疏松
Abstract:
Osteoporosis is a bone disease characterizedlow bone mass and deteriorated bone microstructure, which could be related to the disorders of energy metabolism and bone senescence. Silent mating-type information regulator 2 homolog 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase that regulates cell senescence, energy metabolism and bone remodeling. SIRT1 could be activated not onlyadenosine 5-monophosphate (AMP)-activated protein kinase (AMPK), c-Jun N-terminal kinase 1 (JNK1) and casein kinase 2 (CK2), but alsosmall-molecular drugs such as resveratrol. All these kinases and drugs can affect bone metabolism. Recent findings indicate that SIRT1 signaling pathway plays a direct role in bone metabolism, but the underlying mechanism remains unclear. This paper reviews the structure and function of SIRT1, and the role of SIRT1 in bone metabolism, and discusses the potential of SIRT1 signaling pathway as a new therapeutic target in osteoporosis.
Key words: silent mating-type information regulator 2 homolog 1 (SIRT1), deacetylation, bone metabolism, osteoporosis


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