Oxidative Stress by Monoamine Oxidase Mediates Receptor-Independent Cardiomyocyte Apoptosis by Serotonin and Postischemic Myocardial Injury
作者： Pascale Bianchi , Oxana Kunduzova , Emanuela Masini , Claudie Cambon , Daniele Bani
DOI: 10.1161/CIRCULATIONAHA.104.528133
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摘要: Background— Serotonin (5-hydroxytryptamine [5-HT]), released by activated platelets during cardiac ischemia, is metabolized the mitochondrial enzyme monoamine oxidase A (MAO-A). Because hydrogen peroxide one of byproducts 5-HT degradation MAO-A, we investigated potential role reactive oxygen species generated MAOs in 5-HT-dependent cardiomyocyte death and post-ischemia-reperfusion damage. Methods Results— Treatment isolated adult rat cardiomyocytes with induced intracellular oxidative stress cell apoptosis. The apoptotic cascade triggered involves release cytochrome c, upregulation proapoptotic Bax protein, downregulation antiapoptotic Bcl-2 protein. These effects were prevented inhibition amine transporter or MAO, antioxidants, iron chelation. In contrast, apoptosis was only slightly affected 5-HT2B receptor antagonist SB 206553. vivo, MAO-A largely reduced myocardial ultrastructural dama...
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