Identification of Hsc70 as target for AGE modification in senescent human fibroblasts.
Cellular senescence is known as a potent mechanism of tumor suppression, and cellular senescence in vitro also reflects at least some features of aging in vivo. The Free Radical Theory of aging suggests that reactive oxygen species are important causative agents of aging and cellular senescence. Besides damage of nucleic acids and lipids, also oxidative modifications of proteins have been described as potential causative events in the senescence response. However, the identity of protein targets for post-translational modifications in senescent cells has remained unclear. In the present communication, we analyzed the occurrence of oxidative posttranslational modifications in senescent human endothelial cells and dermal fibroblasts. We found a significant increase in the level of protein carbonyls and AGE modification with senescence in both cell types. Using 2D-Gel electrophoresis and Western Blot we found that heat shock cognate protein 70 is a bona fide target for AGE modification in human fibroblasts.
Unterluggauer
Hermann
H
Institute for Biomedical Aging Research, Austrian Academy of Sciences, Rennweg 10, 6020, Innsbruck, Austria.
Micutkova
Lucia
L
Lindner
Herbert
H
Sarg
Bettina
B
Hernebring
Malin
M
Nystrom
Thomas
T
Jansen-Dürr
Pidder
P
D002478:Cells, Cultured; D016922:Cellular Senescence; D042783:Endothelial Cells / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D050050:Protein Carbonylation; D011499:Protein Processing, Post-Translational
D017127:Glycation End Products, Advanced; D050883:HSC70 Heat-Shock Proteins; C494371:HSPA8 protein, human