Mild heat stress stimulates 20S proteasome and its 11S activator in human fibroblasts undergoing aging in vitro.
Repeated mild heat shock (RMHS) has been shown to have several beneficial hormetic effects on human skin fibroblast undergoing aging in vitro. Because an age-related decline in proteasome activity is 1 of the reasons for the accumulation of abnormal proteins during aging, we have investigated the effects of RMHS on the 20S proteasome, which is the major proteolytic system involved in the removal of abnormal and oxidatively damaged proteins. Serially passaged human skin fibroblasts exposed to RMHS at 41 degrees C for 60 minutes twice a week had increased 3 proteasomal activities by 40% to 95% in early- and midpassage cultures. RMHS-treated cells also contained a 2-fold higher amount of the proteasome activator 11S, and the extent of the bound activator was double in early- and midpassage cells only. Furthermore, there was no difference in the content of the 19S proteasome regulator in the stressed and the unstressed cells. Therefore, RMHS-induced proteasome stimulation in early- and midpassage fibroblasts appears to be due to an induction and enhanced binding of 11S proteasome activators. In contrast to this, the proteasomal system in late-passage senescent cells appears to be less responsive to the stimulatory effects of mild heat shock.
Laboratory of Cellular Ageing, Danish Centre for Molecular Gerontology, Department of Molecular Biology, University of Aarhus, Gustav Wieds Vej 10-C, DK-8000 Aarhus-C, Denmark.
Rasmus
R
Beedholm
Brian F C
BF
Clark
Suresh I S
SI
Rattan
D000251:Adenosine Triphosphatases / Q000032:analysis / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D002850:Chromatography, Gel; D010450:Endopeptidases / Q000032:analysis / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D018869:Heat-Shock Response / Q000502:physiology*; D006801:Humans; D009842:Oligopeptides / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000032:analysis / Q000378:metabolism*; D011485:Protein Binding; D013379:Substrate Specificity
D009842:Oligopeptides; D010450:Endopeptidases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; C119011:26S proteasome non-ATPase regulatory subunit 13; D000251:Adenosine Triphosphatases