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Increased resistanc...
Increased resistance of lipofuscin-loaded prematurely senescent fibroblasts to starvation-induced programmed cell death
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- Stroikin, Yuri (författare)
- Linköpings universitet,Experimentell patologi,Hälsouniversitetet
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- Johansson, Uno (författare)
- Linköpings universitet,Experimentell patologi,Hälsouniversitetet
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- Asplund, Sofia (författare)
- Linköpings universitet,Experimentell patologi,Hälsouniversitetet
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- Öllinger, Karin (författare)
- Linköpings universitet,Experimentell patologi,Hälsouniversitetet
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(creator_code:org_t)
- 2006-07-19
- 2007
- Engelska.
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Ingår i: Biogerontology (Dordrecht). - : Springer Science and Business Media LLC. - 1389-5729 .- 1573-6768. ; 8:1, s. 43-53
- Relaterad länk:
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http://urn.kb.se/res...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Alterations of cellular structures often found in ageing cells is mainly the result of production of reactive oxygen species and a consequence of aerobic life. Both oxidative stress and decreased degradative capacity of lysosomal system cause accumulation of intralysosomal age-related pigment called lipofuscin. To investigate the influence of lipofuscin on cell function, we compared survival of lipofuscin-loaded and control human fibroblasts following complete starvation induced by exposure to phosphate-buffered saline (PBS). Starving of control fibroblasts resulted in lysosomal alkalinisation, relocation of cathepsin D to the cytosol, caspase-3 activation and, finally, cell death, which became evident 72 h after the start of exposure to PBS. Increase of lysosomal pH was significantly less prominent in lipofuscin-loaded cells than in controls and was accompanied neither by leakage of cathepsin D nor by caspase-3 activation even 96 h after the initiation of starvation. Suppression of autophagy by 3-methyladenine (3-MA) accelerated cell death, while inhibition of cathepsin D delayed it, implying an important role of autophagy in cell survival during starvation and showing the involvement of lysosomes in starvation-induced cell death. Disturbed apoptotic response found in lipofuscin-loaded cells can be interpreted as an example of hormesis—an adaptation to low doses of otherwise harmful agents, in this case of lipofuscin, which has a protective effect at moderate amounts but becomes toxic at large quantities.
Nyckelord
- Ageing
- Apoptosis
- Autophagy
- Cathepsin D
- Hormesis
- Lysosomal pH
- 3-Methyladenine
- Pepstatin A
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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