The peptide methionine sulfoxide reductases, MsrA and MsrB (hCBS-1), are downregulated during replicative senescence of human WI-38 fibroblasts.
In contrast to other oxidative modifications of amino acids, methionine sulfoxide can be enzymatically reduced back to methionine in proteins by the peptide methionine sulfoxide reductase system, composed of MsrA and MsrB. The expression of MsrA and one member of the MsrB family, hCBS-1, was analyzed during replicative senescence of WI-38 human fibroblasts. Gene expression decreased for both enzymes in senescent cells compared to young cells, and this decline was associated with an alteration in catalytic activity and the accumulation of oxidized proteins during senescence. These results suggest that downregulation of MsrA and hCBS-1 can alter the ability of senescent cells to cope with oxidative stress, hence contributing to the age-related accumulation of oxidative damage.
Picot
Cédric R
CR
Laboratoire de Biologie et Biochimie Cellulaire du Vieillissement, Université Paris 7-Denis Diderot, 2 place Jussieu, Tour 33-23, CC 7128, 75251 Paris Cedex 05, France.
Perichon
Martine
M
Cintrat
Jean-Christophe
JC
Friguet
Bertrand
B
Petropoulos
Isabelle
I
D002460:Cell Line; D016922:Cellular Senescence; D015536:Down-Regulation; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051150:Methionine Sulfoxide Reductases; D008840:Microfilament Proteins; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D008840:Microfilament Proteins; D016877:Oxidants; D014157:Transcription Factors; D006861:Hydrogen Peroxide; D010088:Oxidoreductases; C120376:MSRB2 protein, human; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase