Shchedrina Valentina A, Vorbrüggen Gerd, Lee Byung Cheon, Kim Hwa-Young, Kabil Hadise, Harshman Lawrence G, Gladyshev Vadim N
Department of Biochemistry and Redox Biology Center, University of Nebraska, Lincoln, NE 68588, USA.
Mech Ageing Dev. 2009 Jul;130(7):429-43. doi: 10.1016/j.mad.2009.04.003. Epub 2009 May 3.
Methionine sulfoxide reductases (Msrs) are enzymes that repair oxidized methionine residues in proteins. This function implicated Msrs in antioxidant defense and the regulation of aging. There are two known Msr types in animals: MsrA specific for the reduction of methionine-S-sulfoxide, and MsrB that catalyzes the reduction of methionine-R-sulfoxide. In a previous study, overexpression of MsrA in the nervous system of Drosophila was found to extend lifespan by 70%. Overexpression of MsrA in yeast also extended lifespan, whereas MsrB overexpression did so only under calorie restriction conditions. The effect of MsrB overexpression on lifespan has not yet been characterized in animal model systems. Here, the GAL4-UAS binary system was used to drive overexpression of cytosolic Drosophila MsrB and mitochondrial mouse MsrB2 in whole body, fatbody, and the nervous system of flies. In contrast to MsrA, MsrB overexpression had no consistent effect on the lifespan of fruit flies on either corn meal or sugar yeast diets. Physical activity, fecundity, and stress resistance were also similar in MsrB-overexpressing and control flies. Thus, MsrA and MsrB, the two proteins with similar function in antioxidant protein repair, have different effects on aging in fruit flies.
甲硫氨酸亚砜还原酶(Msrs)是修复蛋白质中氧化甲硫氨酸残基的酶。该功能表明Msrs参与抗氧化防御和衰老调控。动物中已知有两种Msr类型:特异性还原甲硫氨酸-S-亚砜的MsrA,以及催化甲硫氨酸-R-亚砜还原的MsrB。在先前的一项研究中,发现果蝇神经系统中MsrA的过表达可使寿命延长70%。酵母中MsrA的过表达也能延长寿命,而MsrB的过表达仅在热量限制条件下才会如此。MsrB过表达对寿命的影响在动物模型系统中尚未得到表征。在此,利用GAL4-UAS二元系统在果蝇的全身、脂肪体和神经系统中驱动胞质果蝇MsrB和线粒体小鼠MsrB2的过表达。与MsrA不同,MsrB过表达对以玉米粉或糖酵母为食的果蝇寿命没有一致的影响。MsrB过表达果蝇和对照果蝇的身体活动、繁殖力和抗应激能力也相似。因此,在抗氧化蛋白修复中具有相似功能的两种蛋白质MsrA和MsrB,对果蝇衰老具有不同的影响。