Role of NOX2 in mediating doxorubicin-induced senescence in human endothelial progenitor cells
| Autor: | Roberto Monticolo, Francesco Equitani, Albino Carrizzo, Speranza Rubattu, Sebastiano Sciarretta, Francesca Pagano, Carmine Vecchione, Elena De Falco, Antonella Bordin, Roberto Carnevale, Isotta Chimenti, Camilla Siciliano, Giacomo Frati, Mariangela Peruzzi, Luca Fianchini |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Premature aging Senescence Oxidative phosphorylation Pharmacology Isoprostanes aging cardiovascular diseases doxorubicin endothelial progenitor cells Nox2 developmental biology Nitric oxide 03 medical and health sciences chemistry.chemical_compound Medicine Humans Doxorubicin Progenitor cell Cells Cultured Cellular Senescence Endothelial Progenitor Cells Cardiotoxicity business.industry Interleukin-6 030104 developmental biology chemistry embryonic structures Apocynin NADPH Oxidase 2 cardiovascular system business circulatory and respiratory physiology medicine.drug |
| Zdroj: | Mechanisms of ageing and development. 159 |
| ISSN: | 1872-6216 |
| Popis: | Senescence exerts a great impact on both biological and functional properties of circulating endothelial progenitor cells (EPCs), especially in cardiovascular diseases where the physiological process of aging is accelerated upon clinical administration of certain drugs such as doxorubicin. EPC impairment contributes to doxorubicin-induced cardiotoxicity. Doxorubicin accelerates EPC aging, although mechanisms underlying this phenomenon remain to be fully clarified. Here we investigated if Nox2 activity is able to modulate the premature senescence induced in vitro by doxorubicin in human EPCs. Results showed that in conditioned media obtained from late EPC cultures, the levels of interleukin-6, isoprostanes and nitric oxide bioavailability were increased and reduced respectively after 3h of doxorubicin treatment. These derangements returned to physiological levels when cells were co-treated with apocynin or gp91ds-tat (antioxidant and specific Nox2 inhibitors, respectively). Accordingly, Nox2 activity resulted to be activated by doxorubicin. Importantly, we found that Nox2 inhibition reduced doxorubicin-induced EPC senescence, as indicated by a lower percentage of β-gal positive EPCs. In conclusion, Nox2 activity efficiently contributes to the mechanism of oxidative stress-induced increase in premature aging conferred by doxorubicin. The importance of modulation of Nox2 in human EPCs could reveal a useful tool to restore EPC physiological function and properties. |
| Databáze: | OpenAIRE |
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