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

Abstract

Ksiazek K, Mikula-Pietrasik J, Olijslagers S, Jörres 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-␤-galactosidase and cell cycle inhibitors p16INK4a and p21 WAF1 . Moreover, almost 3 times as many earlypassage 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. DNA damage; peritoneal mesothelial cells CELLULAR SENESCENCE IS A STATE in which somatic cells stop dividing and acquire properties that distinguish them clearly from both proliferating and quiescent cells. The senescence phenotype includes irreversible growth arrest in G 1 phase of the cell cycle, hypertrophic morphology, increased expression of senescence-associated ␤-galactosidase (SA-␤-Gal), accumulation of senescence-associated DNA damage foci and increased expression of cell-cycle inhibitors p16INK4a and p21 WAF1

Iscador Qu inhibits doxorubicin-induced senescence of MCF7 cells

“…SASP components contributing to relapse and aggressive cancer occurrence 22 include: interleukins 6 and 8 (IL-6, IL-8) 23 ; amphiregulin (AREG) and growth-related oncogene (GRO) α 24, 25 , VEGF 26, 27 or matrix metalloproteinases (MMPs) 25, 28, 29 . SASP has recently been linked to immune surveillance of damaged normal and tumor cells 30–32 .…”

Specificity of cytochemical and fluorescence methods of senescence-associated β-galactosidase detection for ageing driven by replication and time

“…Afterwards they were harvested by trypsinization, counted again and subjected to fluorescence analysis based on measurement of the rate of conversion of 4-methylumbelliferyl-β-D-galactopyranose (MUG) to 4-methylumbelliferone (4-MU), as described by Gary and Kindell (2005). The results obtained using the fluorescence method were normalized per cell autofluorescence level, which could be related to the presence and senescence-associated increase in the lipofuscin content (Ksiazek et al 2009b). …”

Cellular senescence and the senescent secretory phenotype: therapeutic opportunities

“…Several processes have been identified that cause or are associated with cellular senescence, all of which also increase with age ( Figure 3). Senescence-causing inducers include repeated cell division and strong mitogenic signals, telomere shortening, DNA damage and mutations, protein aggregation, and increased ROS (46,(56)(57)(58)(59)(60). These insults activate the p53 and p16 INK4a tumor suppressor pathways and potentially other pathways that initiate a senescence response.…”