Accelerated Aging during Chronic Oxidative Stress: A Role for PARP-1
| Autor: | Aalt Bast, Joyce M. J. de Vos-Houben, Gertjan J.M. den Hartog, Leen Timmermans, Geja J. Hageman, Daniëlle M. P. H. J. Boesten |
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| Přispěvatelé: | RS: NUTRIM - R3 - Chronic inflammatory disease and wasting, Farmacologie en Toxicologie, Toxicogenomics, RS: CARIM School for Cardiovascular Diseases |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Aging
Telomerase Poly Adenosine Diphosphate Ribose Cell division Article Subject Flavonols Poly (ADP-Ribose) Polymerase-1 Minocycline Biology medicine.disease_cause Biochemistry chemistry.chemical_compound Telomere Homeostasis tert-Butylhydroperoxide medicine Humans lcsh:QH573-671 Cellular Senescence Flavonoids lcsh:Cytology Cell Biology General Medicine Hydrogen Peroxide DNA Methylation Fibroblasts Telomere Molecular biology Cell biology Oxidative Stress chemistry Chromosomes Human Pair 2 DNA methylation Poly(ADP-ribose) Polymerases Cell aging Fisetin Oxidative stress HeLa Cells Research Article |
| Zdroj: | Oxidative Medicine and Cellular Longevity, Vol 2013 (2013) Oxidative Medicine and Cellular Longevity, 2013:680414. Hindawi Publishing Corporation Oxidative Medicine and Cellular Longevity |
| ISSN: | 1942-0994 1942-0900 |
| Popis: | Oxidative stress plays a major role in the pathophysiology of chronic inflammatory disease and it has also been linked to accelerated telomere shortening. Telomeres are specialized structures at the ends of linear chromosomes that protect these ends from degradation and fusion. Telomeres shorten with each cell division eventually leading to cellular senescence. Research has shown that poly(ADP-ribose) polymerase-1 (PARP-1) and subtelomeric methylation play a role in telomere stability. We hypothesized that PARP-1 plays a role in accelerated aging in chronic inflammatory diseases due to its role as coactivator of NF-κb and AP-1. Therefore we evaluated the effect of chronic PARP-1 inhibition (by fisetin and minocycline) in human fibroblasts (HF) cultured under normal conditions and under conditions of chronic oxidative stress, induced bytert-butyl hydroperoxide (t-BHP). Results showed that PARP-1 inhibition under normal culturing conditions accelerated the rate of telomere shortening. However, under conditions of chronic oxidative stress, PARP-1 inhibition did not show accelerated telomere shortening. We also observed a strong correlation between telomere length and subtelomeric methylation status of HF cells. We conclude that chronic PARP-1 inhibition appears to be beneficial in conditions of chronic oxidative stress but may be detrimental under relatively normal conditions. |
| Databáze: | OpenAIRE |
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