Cited by 234Genomics, phytochemicals, and oxidative stressTelomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model Organisms

Nuclear erythroid factor 2-mediated proteasome activation delays senescence in human fibroblasts

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Kapeta, Suzanne, Chondrogianni, Niki, Gonos, Efstathios S.·2010·Journal of Biological Chemistry

Abstract

Replicative senescence in human fibroblasts is accompanied with alterations of various biological processes, including the impaired function of the proteasome. The proteasome is responsible for the removal of both normal and damaged proteins. Due to its latter function, proteasome is also considered a representative secondary antioxidant cellular mechanism. Nrf2 is a basic transcription factor responsible for the regulation of the cellular antioxidant response that has also been shown to regulate several proteasome subunits in mice. We have established in this study the proteasome-related function of Nrf2 in human fibroblasts undergoing replicative senescence. We demonstrate that Nrf2 has a declined function in senescence, whereas its silencing leads to premature senescence. However, upon its activation by a novel Nrf2 inducer, elevated levels of proteasome activity and content are recorded only in cell lines possessing a functional Nrf2. Moreover, treatment by the Nrf2 inducer results in the enhanced survival of cells following oxidative stress, whereas continuous treatment leads to lifespan extension of human fibroblasts. Importantly the Nrf2-proteasome axis is functional in terminally senescent cultures as these cells retain their responsiveness to the Nrf2 stimuli. In conclusion, these findings open up new directions for future manipulation of the senescence phenotype.

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Crossref · 10.1074/jbc.m109.031575

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Authors
Kapeta, S., Chondrogianni, N., & Gonos, E. S.
Affiliations
National Hellenic Research Foundation (GR)
Corresponding author
  • Chondrogianni, Niki
  • Gonos, Efstathios S.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2010-03
Volume
285
Issue
11
Pages
8171-8184
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2075571292
Cited by
234
References
59
Citations by year
2026: 11 · 2025: 12 · 2024: 20 · 2023: 14 · 2022: 19 · 2021: 13 · 2020: 23 · 2019: 16 · 2018: 15 · 2017: 20 · 2016: 15 · 2015: 8 · 2014: 16 · 2013: 7 · 2012: 13
FWCI
4.17
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • National Hellenic Research Foundation Helios Repository (National Hellenic Research Foundation) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords
Nrf2, proteasome, replicative senescence, human fibroblasts, premature senescence, Nrf2 inducers, oxidative stress, lifespan extension, protein degradation, senescence reversal
MeSH terms
Cell Division, Cell Line, Enzyme Activation, Fibroblasts, Glycyrrhetinic Acid, Humans, Luciferases, Down-Regulation, Cellular Senescence, Reactive Oxygen Species, Oxidative Stress, RNA Interference, Proteasome Endopeptidase Complex, NF-E2-Related Factor 2

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