Artículo de revista
Trimetazidine prevents palmitate-induced mitochondrial fission and dysfunction in cultured cardiomyocytes
Fecha
2014Registro en:
Biochemical Pharmacology, Volumen 91, Issue 3, 2018, Pages 323-336
18732968
00062952
10.1016/j.bcp.2014.07.022
Autor
Kuzmicic Previtali, Jovan Paolo
Parra, Valentina
Verdejo, Hugo E.
López Crisosto, Camila
Chiong Lay, Mario
García Nannig, Lorena
Jensen, Michael D.
Bernlohr, David A.
Castro, Pablo F.
Lavandero González, Sergio
Institución
Resumen
© 2014 Elsevier Inc. All rights reserved. Metabolic and cardiovascular disease patients have increased plasma levels of lipids and, specifically, of palmitate, which can be toxic for several tissues. Trimetazidine (TMZ), a partial inhibitor of lipid oxidation, has been proposed as a metabolic modulator for several cardiovascular pathologies. However, its mechanism of action is controversial. Given the fact that TMZ is able to alter mitochondrial metabolism, we evaluated the protective role of TMZ on mitochondrial morphology and function in an in vitro model of lipotoxicity induced by palmitate. We treated cultured rat cardiomyocytes with BSA-conjugated palmitate (25 nM free), TMZ (0.1-100 μM), or a combination of both. We evaluated mitochondrial morphology and lipid accumulation by confocal fluorescence microscopy, parameters of mitochondrial metabolism (mitochondrial membrane potential, oxygen consumption rate [OCR], and ATP levels), and ceramide production by mass spectrometry and in