Failure of stress-induced downregulation of Bcl-2 contributes to apoptosis resistance in senescent human diploid fibroblasts
Abstract
We previously reported that senescent human diploid fibroblasts (HDFs) are resistant to apoptosis induced by H(2)O(2) and staurosporine. We report here that senescent HDFs are resistant to thapsigargin-induced apoptosis as well. These agonists caused the reductions in mitochondrial membrane potential (MMP) and in the apoptosis inhibitory protein (B-cell lymphoma) only in young HDFs but not in senescent HDFs. In addition, downregulation of Bcl-2 increased the sensitivity of senescent HDFs to apoptosis induction, suggesting the significant role of Bcl-2 in apoptosis resistance of the senescent HDFs. We further found that P-cAMP response element-binding protein (CREB), a positive regulator of Bcl-2, decreased in stress-induced apoptosis of young HDFs but not in senescent HDFs, and that Bcl-2 was markedly reduced in CREB small interfering RNA (siRNA), transfected senescent HDFs. In addition, activity of protein phosphatase 2A (PP2A), which dephosphorylates p-CREB, significantly increased in young HDFs but not in senescent HDFs treated with H(2)O(2), staurosporine or thapsigargin. Taken together, these results suggest that failure of stress-induced downregulation of Bcl-2 underlies resistance of senescent HDFs to apoptosis.
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Senescent cells are resistant to apoptosis.
“senescent cells are resistant to apoptosis”
From Skeletal muscle aging, cellular senescence, and senotherapeutics: current knowledge and future directions (2021) · cites this paper as Ryu et al., 2007
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Self-citation
- Authors
- Ryu, S. J., Oh, Y. S., & Park, S. C.
- Affiliations
- Seoul National University (KR)
- Corresponding author
- Park, S C
- ORCID
- Oh, Y S
- Venue
- Cell Death & Differentiation
- Published
- 2007-02-09
- Volume
- 14
- Issue
- 5
- Pages
- 1020-1028
- ISSN
- 1350-9047 (ISSN-L)
- 1476-5403
- OpenAlex
- W2084484454
- Cited by
- 114
- References
- 38
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 15 · 2023: 15 · 2022: 8 · 2021: 17 · 2020: 9 · 2019: 3 · 2018: 5 · 2017: 2 · 2016: 3 · 2015: 5 · 2014: 3 · 2013: 2 · 2012: 4
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cell Death and Differentiation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Korea Science and Engineering Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- cellular senescence, apoptosis resistance, Bcl-2 downregulation, human diploid fibroblasts, staurosporine, hydrogen peroxide, CREB, protein phosphatase 2A, mitochondrial membrane potential, stress-induced apoptosis
- MeSH terms
- Cells, Cultured, Diploidy, Fibroblasts, Humans, Hydrogen Peroxide, Phosphoprotein Phosphatases, Phosphoproteins, Down-Regulation, Cellular Senescence, Apoptosis, Cyclic AMP Response Element-Binding Protein, Proto-Oncogene Proteins c-bcl-2, Thapsigargin, Staurosporine, Membrane Potential, Mitochondrial, Protein Phosphatase 2
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