蛋氨酸亚砜还原酶及其在白内障发生发展中的作用

蛋氨酸(Met)是生物体内很容易被氧化的氨基酸之一,氧化应激条件下,生成S型和R型蛋氨酸亚砜(MetO), 晶状体蛋白中MetO的增加与晶状体老化和白内障形成相关。生物体内存在着两种不同的蛋氨酸亚砜还原酶(Msr),即MsrA和B,分别能特异性地作用于自由或结合在蛋白质中的S-MetO和R-MetO,将MetO修复为Met,从而避免了蛋白质结构和功能的改变。在哺乳动物中,MsrA以单基因形式存在,而MsrB有3种异构体,分别为MsrB1,MsrB2和MsrB3,其中MsrB1是一个硒蛋白,又被称为硒蛋白R(SelR)。本文介绍了Msrs的基因表达、分布和亚细胞定位,比较了MsrA和MsrBs蛋白结构和催化机制的异同,讨论了晶状体蛋白Met残基的氧化与白内障形成和发展的关系。现有的这些研究结果表明Msrs作为一类特异性的抗氧化还原酶,通过对MetO的修复,在抑制晶状体的损伤方面发挥重要作用。此外,MsrB1作为一个硒蛋白受机体硒水平的调节,因此,通过补硒保持晶状体适当的硒浓度以维持MsrB1的活性,对白内障的形成和发展可能具有一定的预防作用。

Methionine Sulfoxide Reductase and Their Roles in Cataracts Formation and Development

Methionine(Met) is one of the most easily oxidized amino acids and undergoes reversible oxidation,leading to the formation of S-and R-methionine sulfoxide(MetO).An increase of protein MetO is related to the aging of lens aging and formation of cataract.In organisms there are two classes of methionine sulfoxide reductases(Msrs),MsrA and MsrB,that can stereospecifically catalyze the thioredoxin-dependent reduction of free and protein-bound S-and R-MetO to Met,respectively,thus maintaining the structure and function of the proteins.There are one MsrA and three MsrBs(MsrB1,MsrB2 and MsrB3) in mammals.MsrB1 is a selenoprotein,named selenoprotein R(SelR).In this review,we introduced the gene expressions,distribution and subcellular localization of Msrs,compared their differences on protein structures and the possible catalytic mechanisms between MsrA and MsrBs,and discussed the relationship of oxidation of Met residues in lens proteins with cataract formation.These research progresses suggest that the Msrs as antioxidative reductases may play an important role in restraining the lens damage by reducing MetO to Met.In addition,because MsrB1 as only one selenoprotein is regulated by selenium level,appropriate selenium levels in lens by selenium supplementation in order to maintain MsrB1 activity may be beneficial for prevention cataract formation and development.