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Premature senescence of mesothelial cells is associated with non-telomeric DNA damage

Lookup NU author(s): Dr Joao Passos, Dr Sharon Olijslagers, Dr Gabriele Saretzki, Dr Carmen Martin-Ruiz, Professor Thomas von Zglinicki

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Abstract

Human peritoneal mesothelial cells (HPMCs) senesce in vitro after barely few population doublings. In this report, we show that senescence of HPMCs is associated with increased accumulation of γ-H2A.X foci, which reveal DNA double-strand breaks. Of note, already early-passage cultures contain a considerable fraction (44 ± 10%) of cells bearing γ-H2A.X foci. The γ-H2A.X foci localize predominantly to non-telomeric DNA, either in young or senescent cells. Moreover, HPMCs seem to have unusually short telomeres (∼3.5 kbp) despite the presence of active telomerase. These telomeres do not shorten during senescence, but the activity of telomerase decreases to undetectable levels. In addition, senescence of HPMCs is associated with mitochondrial dysfunction, as manifested by increased production of reactive oxygen species and reduced mitochondrial membrane potential. These results may indicate that premature senescence of HPMCs is largely related to oxidative stress-induced DNA damage in non-telomeric regions of the genome. © 2007 Elsevier Inc. All rights reserved.


Publication metadata

Author(s): Ksiazek K, Passos JF, Olijslagers S, Saretzki G, Martin-Ruiz C, von Zglinicki T

Publication type: Article

Publication status: Published

Journal: Biochemical and Biophysical Research Communications

Year: 2007

Volume: 362

Issue: 3

Pages: 707-711

ISSN (print): 0006-291X

ISSN (electronic): 1090-2104

Publisher: Academic Press

URL: http://dx.doi.org/10.1016/j.bbrc.2007.08.047

DOI: 10.1016/j.bbrc.2007.08.047

PubMed id: 17720141


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