Methionine sulfoxide reductase (MsrA) is a regulator of antioxidant defense and lifespan in mammals
Methionine sulfoxide reductase (MsrA) is a regulator of antioxidant defense and lifespan in mammals
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DOI：
10.1073/pnas.231472998
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发表时间：
2001-11-06
影响因子：
11.1
通讯作者：
Stadtman, ER
中科院分区：
文献类型：
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作者：
Moskovitz, J;Bar-Noy, S;Stadtman, ER
活性氧对蛋白质的氧化作用与衰老、氧化应激以及许多疾病相关。尽管游离的和与蛋白质结合的甲硫氨酸残基对氧化为甲硫氨酸亚砜衍生物尤为敏感，但这些氧化作用可通过甲硫氨酸亚砜还原酶（MsrA）的作用轻易修复。为了更好地理解MsrA在新陈代谢中的生物学作用，我们培育出了一种缺乏MsrA基因的小鼠品系。与野生型相比，这种突变体：（i）对氧化应激（暴露于100%氧气中）表现出更强的敏感性；（ii）在正常和高氧条件下寿命都更短；（iii）在6个月大之后出现非典型的（踮脚）行走模式；（iv）在氧化应激下组织中氧化蛋白质（羰基衍生物）的积累水平更高；（v）在氧化应激下上调硫氧还蛋白还原酶表达的能力较弱。因此，MsrA似乎在衰老和神经系统疾病中可能起着重要作用。
Oxidation of proteins by reactive oxygen species is associated with aging, oxidative stress, and many diseases. Although free and protein-bound methionine residues are particularly sensitive to oxidation to methionine sulfoxide derivatives, these oxidations are readily repaired by the action of methionine sulfoxide reductase (MsrA). To gain a better understanding of the biological roles of MsrA in metabolism, we have created a strain of mouse that lacks the MsrA gene. Compared with the wild type, this mutant: (i) exhibits enhanced sensitivity to oxidative stress (exposure to 100% oxygen); (ii) has a shorter lifespan under both normal and hyperoxic conditions; (iii) develops an atypical (tip-toe) walking pattern after 6 months of age; (iv) accumulates higher tissue levels of oxidized protein (carbonyl derivatives) under oxidative stress; and (v) is less able to up-regulate expression of thioredoxin reductase under oxidative stress. It thus seems that MsrA may play an important role in aging and neurological disorders.