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http://repositorio.pediatria.gob.mx:8180/handle/20.500.12103/1681| Título : | Antineoplastic copper coordinated complexes (Casiopeinas) uncouple oxidative phosphorylation and induce mitochondrial permeability transition in cardiac mitochondria and cardiomyocytes |
| Creador: | Silva Platas, C |
| Nivel de acceso: | Open access |
| Palabras clave : | Animales Antineoplásicos - Efectos adversos Antineoplásicos - farmacología Cobre - Efectos adversos Cobre - farmacología Mitocondrias Cardíacas - metabolismo Mitocondrias Cardíacas - patología Membranas Mitocondriales - Efectos de drogas Miocitos Cardíacos - metabolismo Miocitos Cardíacos - patología Fosforilación Oxidativa - Efectos de drogas Permeabilidad - Efectos de drogas Ratas Animals Antineoplastic Agents - adverse effects Antineoplastic Agents - pharmacology Copper - adverse effects Copper - pharmacology Mitochondria, Heart - metabolism Mitochondria, Heart - pathology Mitochondrial Membranes - drug effects Myocytes, Cardiac - metabolism Myocytes, Cardiac - pathology Oxidative Phosphorylation - drug effects Permeability - drug effects Rats Antineoplásico Miocitos Cardíacos Cardiotoxicidad Casiopeinas Mitocondrias Poro de transición de permeabilidad Antineoplastic Cardiomyocytes Cardiotoxicity Casiopeinas Mitochondria Permeability transition pore |
| Descripción : | Copper-based drugs, Casiopeinas (Cas), exhibit antiproliferative and antineoplastic activities in vitro and in vivo, respectively. Unfortunately, the clinical use of these novel chemotherapeutics could be limited by the development of dose-dependent cardiotoxicity. In addition, the molecular mechanisms underlying Cas cardiotoxicity and anticancer activity are not completely understood. Here, we explore the potential impact of Cas on the cardiac mitochondria energetics as the molecular mechanisms underlying Cas-induced cardiotoxicity. To explore the properties on mitochondrial metabolism, we determined Cas effects on respiration, membrane potential, membrane permeability, and redox state in isolated cardiac mitochondria. The effect of Cas on the mitochondrial membrane potential (Δψm) was also evaluated in isolated cardiomyocytes by confocal microscopy and flow cytometry. Cas IIIEa, IIgly, and IIIia predominately inhibited maximal NADH- and succinate-linked mitochondrial respiration, increased the state-4 respiration rate and reduced membrane potential, suggesting that Cas also act as mitochondrial uncouplers. Interestingly, cyclosporine A inhibited Cas-induced mitochondrial depolarization, suggesting the involvement of mitochondrial permeability transition pore (mPTP). Similarly to isolated mitochondria, in isolated cardiomyocytes, Cas treatment decreased the Δψm and cyclosporine A treatment prevented mitochondrial depolarization. The production of H2O2 increased in Cas-treated mitochondria, which might also increase the oxidation of mitochondrial proteins such as adenine nucleotide translocase. In accordance, an antioxidant scavenger (Tiron) significantly diminished Cas IIIia mitochondrial depolarization. Cas induces a prominent loss of membrane potential, associated with alterations in redox state, which increases mPTP opening, potentially due to thiol-dependent modifications of the pore, suggesting that direct or indirect inhibition of mPTP opening might reduce Cas-induced cardiotoxicity. © 2016, Springer Science+Business Media New York. |
| Colaborador(es) u otros Autores: | Guerrero-Beltrán Carlos Enrique Carrancá Mariana Castillo Elena Cristina Bernal-Ramírez Judith Oropeza-Almazán Yuriana González Lorena N Rojo Rocío Martínez Luis Enrique Valiente-Banuet Juan Ruiz-Azuara Lena Bravo-Gómez María Elena García Noemí Carvajal Karla García-Rivas Gerardo |
| Fecha de publicación : | 2016 |
| Tipo de publicación: | Artículo |
| Formato: | |
| Identificador del Recurso : | 10.1007/s10863-015-9640-x |
| Fuente: | Journal of Bioenergetics and Biomembranes 48(1):43 - 54 |
| URI : | http://repositorio.pediatria.gob.mx:8180/handle/20.500.12103/1681 |
| Idioma: | eng |
| Aparece en las colecciones: | Artículos |
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