Age-related loss of stress-induced nuclear proteasome activation is due to low PARP-1 activity

Edina Bakondi, Betul Catalgol, I. Bak, Tobias Jung, Perinur Bozaykut, Mehmet Bayramicli, Nesrin Kartal Ozer, Tilman Grune

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Changes in protein turnover are among the dominant metabolic changes during aging. Of special importance is the maintenance of nuclear protein homeostasis to ensure a coordinated cellular metabolism. Therefore, in the nucleus a special PARP-1-mediated mechanism of proteasomal activation exists to ensure a rapid degradation of oxidized nuclear proteins. It was already demonstrated earlier that the cytosolic proteasomal system declines dramatically with aging, whereas the nuclear proteasome remains less affected. We demonstrate here that the stress-mediated proteasomal activation in the nucleus declines during replicative senescence of human fibroblasts. Furthermore, we clearly show that this decline in the PARP-1-mediated proteasomal activation is due to a decline in the expression and activity of PARP-1 in senescent fibroblasts. In a final study we show that this process also happens in vivo, because the protein expression level of PARP-1 is significantly lower in the skin of aged donors compared to that of young ones. Therefore, we conclude that the rate-limiting factor in poly(ADP-ribose)-mediated proteasomal activation in oxidative stress is PARP-1 and not the nuclear proteasome itself.

Original languageEnglish
Pages (from-to)86-92
Number of pages7
JournalFree Radical Biology and Medicine
Volume50
Issue number1
DOIs
Publication statusPublished - Jan 1 2011

Fingerprint

Proteasome Endopeptidase Complex
Nuclear Proteins
Fibroblasts
Chemical activation
Poly Adenosine Diphosphate Ribose
Cell Aging
Proteins
Oxidative Stress
Homeostasis
Aging of materials
Maintenance
Skin
Oxidative stress
Metabolism
Degradation

Keywords

  • Aging
  • Free radicals
  • Nucleus
  • PARP
  • Proteasome
  • Protein oxidation

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Age-related loss of stress-induced nuclear proteasome activation is due to low PARP-1 activity. / Bakondi, Edina; Catalgol, Betul; Bak, I.; Jung, Tobias; Bozaykut, Perinur; Bayramicli, Mehmet; Ozer, Nesrin Kartal; Grune, Tilman.

In: Free Radical Biology and Medicine, Vol. 50, No. 1, 01.01.2011, p. 86-92.

Research output: Contribution to journalArticle

Bakondi, Edina ; Catalgol, Betul ; Bak, I. ; Jung, Tobias ; Bozaykut, Perinur ; Bayramicli, Mehmet ; Ozer, Nesrin Kartal ; Grune, Tilman. / Age-related loss of stress-induced nuclear proteasome activation is due to low PARP-1 activity. In: Free Radical Biology and Medicine. 2011 ; Vol. 50, No. 1. pp. 86-92.
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