Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-1-3
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1873-4596
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
86-92
pubmed:meshHeading
pubmed-meshheading:20977936-Aging, pubmed-meshheading:20977936-Benzamides, pubmed-meshheading:20977936-Biopsy, pubmed-meshheading:20977936-Cell Aging, pubmed-meshheading:20977936-Cell Nucleus, pubmed-meshheading:20977936-Cell Proliferation, pubmed-meshheading:20977936-Cell Survival, pubmed-meshheading:20977936-Cells, Cultured, pubmed-meshheading:20977936-Down-Regulation, pubmed-meshheading:20977936-Enzyme Activation, pubmed-meshheading:20977936-Enzyme Inhibitors, pubmed-meshheading:20977936-Fibroblasts, pubmed-meshheading:20977936-Humans, pubmed-meshheading:20977936-Hydrogen Peroxide, pubmed-meshheading:20977936-Oxidative Stress, pubmed-meshheading:20977936-Poly(ADP-ribose) Polymerases, pubmed-meshheading:20977936-Poly Adenosine Diphosphate Ribose, pubmed-meshheading:20977936-Proteasome Endopeptidase Complex
pubmed:year
2011
pubmed:articleTitle
Age-related loss of stress-induced nuclear proteasome activation is due to low PARP-1 activity.
pubmed:affiliation
Institute of Biological Chemistry and Nutrition, Department of Biofunctionality and Food Safety, University of Hohenheim, Stuttgart, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't