Protein oxidative modifications and replicative senescence of WI-38 human embryonic fibroblasts

Ahmed, Emad, Picot, C.R., Bulteau, A.-L., Friguet, B.,


The age-related accumulation of oxidized proteins is dependent on the balance between the generation of oxidatively modified proteins and their elimination by protein degradation and repair systems. Previous studies have demonstrated that replicative senescence represents a valid model of in vitro aging and that senescent cells do accumulate oxidized proteinswhile both proteasome, which is the major intracellular proteolytic system implicated in the removal of abnormal and oxidized proteins, and the oxidized protein-repair enzymes, methionine sulfoxide reductases, are being impaired. Declining proteasome activity with age has been attributed to decreased proteasome subunits expression and/or inactivation upon alteration of proteasome subunits, as well as accumulation of endogeneous inhibitors, such as highly oxidized and cross-linked proteins. To gain further insight into the mechanisms that might be implicated in the decreased activity of the proteasome with replicative senescence, the occurrence of proteins modified by glycoxidation and conjugation by lipid peroxidation products has been investigated in senescent cells. Indeed, such modification as the formation of protein adducts with the lipid peroxidation product 4-hydroxy-2-nonenal can generate cross-linked proteins that become resistant to degradation by the proteasome and can act as inhibitors of the proteasome. Using specific antibodies that recognize glycoxidation and lipid peroxidation adducts on proteins, both modifications were demonstrated and found to increase in senescent cells when compared with young fibroblasts. Moreover, the patterns of modified proteins obtained after separation by SDS gel electrophoresis were indicative of preferential protein targets for both modifications. © 2007 New York Academy of Sciences.

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Title Protein oxidative modifications and replicative senescence of WI-38 human embryonic fibroblasts
Authors Ahmed, Emad ; Picot, C.R. ; Bulteau, A.-L. ; Friguet, B. 
Issue Date 2007
Journal Annals of the New York Academy of Sciences 
PubMed ID 1119
Scopus ID 2-s2.0-36549024455

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