Methionine sulfoxide reductase (MsrA) is a regulator of antioxidant defense and lifespan in mammals.

Authors: Moskovitz J; Bar-Noy S; Williams WM; Requena J; Berlett BS; Stadtman ER

Abstract: 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.

Keywords: Animals; Antioxidants/*metabolism; Cell Line; Gene Targeting; Life Expectancy; Methionine/*chemistry; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Oxidative Stress; Oxidoreductases/chemistry/genetics/*metabolism; Oxidoreductases Acting on Sulfur Group Donors
Journal: Proceedings of the National Academy of Sciences of the United States of America
Volume: 98
Issue: 23
Pages: 12920-5
Date: Oct. 19, 2001
PMID: 11606777
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Citation:

Moskovitz J, Bar-Noy S, Williams WM, Requena J, Berlett BS, Stadtman ER (2001) Methionine sulfoxide reductase (MsrA) is a regulator of antioxidant defense and lifespan in mammals. Proceedings of the National Academy of Sciences of the United States of America 98: 12920-5.


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