Rat peptide methionine sulphoxide reductase: cloning of the cDNA, and down-regulation of gene expression and enzyme activity during aging.
Peptide methionine sulphoxide reductase (PMSR, EC 1.8.4.6), the msrA or pmsR gene product, is a ubiquitous enzyme catalysing the reduction of methionine sulphoxide to methionine in proteins. Decreased expression and/or activity of the PMSR with age could explain, at least in part, the accumulation of oxidized protein observed upon aging. To test this hypothesis, the rat pmsR cDNA was cloned and sequenced. The recombinant protein was expressed, its catalytic activity checked with a synthetic substrate and polyclonal antibodies were raised against recombinant PMSR. The expression of the pmsR gene and protein as well as its catalytic activity were then analysed as a function of age in the rat brain and in two organs that express the most PMSR, liver and kidney. It appears that pmsR gene expression decreases with age in liver and kidney as early as 18 months, whereas protein level and protein activity are reduced in the three organs at the very end of the life of the rat (26 months). These results suggest that the down-regulation of PMSR can contribute to the accumulation of oxidized protein that has been associated with the aging process.
Petropoulos
I
I
Laboratoire de Biologie et Biochimie Cellulaire du Vieillissement, Université Denis Diderot-Paris 7, CC 7128, 2 place Jussieu, 75251 Paris Cedex 05, France.
Mary
J
J
Perichon
M
M
Friguet
B
B
D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002384:Catalysis; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000032:analysis; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008297:Male; D051150:Methionine Sulfoxide Reductases; D008969:Molecular Sequence Data; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D018076:DNA, Complementary; D012333:RNA, Messenger; D011994:Recombinant Proteins; D010088:Oxidoreductases; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase