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Vulnerability to oxidative stress and different patterns of senescence in human peritoneal mesothelial cell strains

Lookup NU author(s): Dr Sharon Olijslagers, Professor Thomas von Zglinicki

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Abstract

Both the ascites fluid-derived mesothelial cell line LP-9 and primary cultures of human omentum-derived mesothelial cells (HOMCs) are commonly used in experimental studies. However, they seem to have a different replicative potential in vitro. In the present study, we have attempted to determine the causes of this discrepancy. HOMCs were found to divide fewer times and enter senescence earlier than LP-9 cells. This effect was coupled with earlier increases in the expression of senescence-associated-β-galactosidase and cell cycle inhibitors p16INK4a and p21WAF1. Moreover, almost 3 times as many early-passage HOMCs as LP-9 cells bore senescence-associated DNA damage foci. In sharp contrast to LP-9 cells, the foci present in HOMCs localized predominantly outside the telomeres, and the HOMC telomere length did not significantly shorten during senescence. Compared with LP-9 cells, HOMCs were found to enter senescence with significantly lower levels of lipofuscin and damaged DNA, and markedly decreased glutathione contents. In addition, early-passage HOMCs generated significantly more reactive oxygen species either spontaneously or in response to exogenous oxidants. These results indicate that compared with LP-9 cells, HOMCs undergo stress-induced telomere-independent premature senescence, which may result from increased vulnerability to oxidative DNA injury. Copyright © 2009 the American Physiological Society.


Publication metadata

Author(s): Ksiazek K, Mikula-Pietrasik J, Olijslagers S, Jörres A, Von Zglinicki T, Witowski J

Publication type: Article

Publication status: Published

Journal: American Journal of Physiology: Regulatory Integrative and Comparative Physiology

Year: 2009

Volume: 296

Issue: 2

Pages: R374-R382

ISSN (print): 0363-6119

ISSN (electronic): 1522-1490

Publisher: American Physiological Society

URL: http://dx.doi.org/10.1152/ajpregu.90451.2008

DOI: 10.1152/ajpregu.90451.2008

PubMed id: 19036828


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