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

Ksiazek K, Mikula-Pietrasik J, Olijslagers S, Jorres A, von Zglinicki T, Witowski J. Vulnerability to oxidative stress and different patterns of senescence in human peritoneal mesothelial cell strains. Am J Physiol Regul Integr Comp Physiol 296: R374-R382, 2009. First published November 26, 2008; doi: 10.1152/ajpregu.90451.2008.-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-beta-galactosidase and cell cycle inhibitors p16(INK4a) and p21(WAF1). 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.