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Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):12920-5. Epub 2001 Oct 23.

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

Author information

1
National Institutes of Health, National Heart Lung and Blood Institute, Laboratory of Biochemistry, Bethesda, MD 20892, USA. moskovij@nhlbi.nih.gov

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.

PMID:
11606777
PMCID:
PMC60800
DOI:
10.1073/pnas.231472998
[Indexed for MEDLINE]
Free PMC Article

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