Age-associated diseases such as neurodegenerative and cardiovascular disorders are characterized by increased oxidative stress associated with autophagy dysfunction. Oleuropein aglycone (OA), the main polyphenol found in olive oil, was recently characterized as an autophagy inducer and a promising agent against neurodegeneration. It is presently unknown whether OA can have beneficial effect in a model of cardiac stress characterized by autophagy dysfunction. Here, we explored the effects of OA in cardiomyocytes with overexpression of monoamine oxidase-A (MAO-A). This enzyme, by degrading catecholamine and serotonin, produces hydrogen peroxide (H2O2) that causes oxidative stress, autophagic flux blockade and cell necrosis. We observed that OA treatment counteracted the cytotoxic effects of MAO-A through autophagy activation, as displayed by the increase of autophagic vacuoles and autophagy-specific markers (Beclin1 and LC3II). Moreover, the decrease of autophagosomes and the increase of autolysosomes, indicative of autophagosome–lysosome fusion, suggested a restoration of the defective autophagic flux. Most interestingly, we found that the ability of OA to confer cardioprotection through autophagy induction involved nuclear translocation and activation of the transcriptional factor-EB (TFEB). Our data provide strong evidence of the beneficial effects of OA suggesting its potential use as a nutraceutical agent against age-related pathologies involving autophagy dysfunction, including cardiovascular diseases.
Oleuropein aglycone protects against MAO-A-induced autophagy impairment and cardiomyocyte death through activation of TFEB / Caterina Miceli, Yohan Santin, Nicola Manzella, Raffaele Coppini, Andrea Berti, Massimo Stefani, Angelo Parini, Jeanne Mialet-Perez, Chiara Nediani. - In: OXIDATIVE MEDICINE AND CELLULAR LONGEVITY. - ISSN 1942-0994. - ELETTRONICO. - 2018:(2018), pp. 0-0. [10.1155/2018/8067592]
Oleuropein aglycone protects against MAO-A-induced autophagy impairment and cardiomyocyte death through activation of TFEB.
Caterina Miceli;Raffaele Coppini;Andrea Berti;Massimo Stefani;Chiara Nediani
2018
Abstract
Age-associated diseases such as neurodegenerative and cardiovascular disorders are characterized by increased oxidative stress associated with autophagy dysfunction. Oleuropein aglycone (OA), the main polyphenol found in olive oil, was recently characterized as an autophagy inducer and a promising agent against neurodegeneration. It is presently unknown whether OA can have beneficial effect in a model of cardiac stress characterized by autophagy dysfunction. Here, we explored the effects of OA in cardiomyocytes with overexpression of monoamine oxidase-A (MAO-A). This enzyme, by degrading catecholamine and serotonin, produces hydrogen peroxide (H2O2) that causes oxidative stress, autophagic flux blockade and cell necrosis. We observed that OA treatment counteracted the cytotoxic effects of MAO-A through autophagy activation, as displayed by the increase of autophagic vacuoles and autophagy-specific markers (Beclin1 and LC3II). Moreover, the decrease of autophagosomes and the increase of autolysosomes, indicative of autophagosome–lysosome fusion, suggested a restoration of the defective autophagic flux. Most interestingly, we found that the ability of OA to confer cardioprotection through autophagy induction involved nuclear translocation and activation of the transcriptional factor-EB (TFEB). Our data provide strong evidence of the beneficial effects of OA suggesting its potential use as a nutraceutical agent against age-related pathologies involving autophagy dysfunction, including cardiovascular diseases.File | Dimensione | Formato | |
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