中性鞘磷脂酶-2的调控机制与功能研究进展

Advance in Research on Regulatory Mechanism and Functions of Neutral Sphingomyelinse 2

中性鞘磷脂酶-2主要分布于哺乳动物细胞质膜,能水解神经鞘磷脂生成神经酰胺,参与细胞凋亡、生长抑制、炎症反应等多种生理病理活动调节,并与阿尔茨海默病的发展、骨骼生长有关。在生理pH值和钙、镁、锰阳离子环境下,氧化应激能诱导中性鞘磷脂酶-2磷酸化调节其活性,鞘磷脂等阴离子脂质以及受体活化的蛋白激酶C1/胚胎外胚层发展蛋白等信号分子的诱导结合也是其活性的重要调节途径。本文主要综述中性鞘磷脂酶-2的结构、功能及其分子机制,揭示其当前研究进展。

Neutral sphingomyelinase 2 （nSMase2）, which located mainly on the plasma membrane, hydrolyzes s tion of cell phingomyelin into ceramide and plays an important role in the physiological and pathological regula- apoptosis, cell growth arrest, and inflammation, nSMase2 is also involved in the development of Alzheimer＇ s disease and the bone growth. Under neutral pH and the presence of Ca2＋ , activity of nSMase2 is induced by oxidative stress through phosphorylation. Furthermore, Mg2＋ , and the induced Mn＋ , the interaction of anionic phospholipids and the signaling molecules like receptor for activated C-kinase 1/embryonic ectodermal development with nSMase2 are also crucial mechanisms of protein activation. In the review, recent research advances in the structure and function of nSMase2 and its underlying mechanisms are summarized.