Increased resistance of lipofuscin-loaded prematurely senescent fibroblasts to starvation-induced programmed cell death
2007 (English)In: Biogerontology (Dordrecht), ISSN 1389-5729, Vol. 8, no 1, 43-53 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2007. Vol. 8, no 1, 43-53 p.
Ageing, Apoptosis, Autophagy, Cathepsin D, Hormesis, Lysosomal pH, 3-Methyladenine, Pepstatin A
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-14213DOI: 10.1007/s10522-006-9029-7OAI: oai:DiVA.org:liu-14213DiVA: diva2:22911