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

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dc.contributor.authorYILMAZ, BETÜL
dc.contributor.authorsBakondi, Edina; Catalgol, Betul; Bak, Istvan; Jung, Tobias; Bozaykut, Perinur; Bayramicli, Mehmet; Ozer, Nesrin Kartal; Grune, Tilman
dc.date.accessioned2022-03-12T18:04:58Z
dc.date.available2022-03-12T18:04:58Z
dc.date.issued2011
dc.description.abstractChanges 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. (C) 2010 Elsevier Inc. All rights reserved.
dc.identifier.doi10.1016/j.freeradbiomed.2010.10.700
dc.identifier.eissn1873-4596
dc.identifier.issn0891-5849
dc.identifier.pubmed20977936
dc.identifier.urihttps://hdl.handle.net/11424/230541
dc.identifier.wosWOS:000286407700009
dc.language.isoeng
dc.publisherELSEVIER SCIENCE INC
dc.relation.ispartofFREE RADICAL BIOLOGY AND MEDICINE
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectProtein oxidation
dc.subjectAging
dc.subjectProteasome
dc.subjectPARP
dc.subjectNucleus
dc.subjectFree radicals
dc.subjectBRAIN PROTEIN OXIDATION
dc.subjectHUMAN MRC-5 FIBROBLASTS
dc.subjectADP-RIBOSE-POLYMERASE
dc.subjectHUMAN BJ FIBROBLASTS
dc.subjectPOLY(ADP-RIBOSE) POLYMERASE
dc.subjectOXIDIZED PROTEINS
dc.subjectCELLULAR SENESCENCE
dc.subjectALZHEIMER-DISEASE
dc.subjectPROLIFERATIVE SENESCENCE
dc.subjectMULTICATALYTIC PROTEASE
dc.titleAge-related loss of stress-induced nuclear proteasome activation is due to low PARP-1 activity
dc.typearticle
dspace.entity.typePublication
local.avesis.idfaaba687-ae74-42a8-8e2c-d405872a48ab
local.import.packageSS17
local.indexed.atWOS
local.indexed.atSCOPUS
local.journal.numberofpages7
oaire.citation.endPage92
oaire.citation.issue1
oaire.citation.startPage86
oaire.citation.titleFREE RADICAL BIOLOGY AND MEDICINE
oaire.citation.volume50
relation.isAuthorOfPublication81633a07-e5fb-4760-b3ef-bf0878d87827
relation.isAuthorOfPublication.latestForDiscovery81633a07-e5fb-4760-b3ef-bf0878d87827

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