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10.1016/j.abb.2016.02.021
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Título: | Early oxidative damage induced by doxorubicin: Source of production, protection by GKT137831 and effect on Ca(2+) transporters in HL-1 cardiomyocytes |
Fecha de publicación: | 2016 |
Cita bibliográfica: | Arch Biochem Biophys. 2016 Mar 15:594:26-36.doi: 10.1016/j.abb.2016.02.021. Epub 2016 Feb 22. |
ISSN: | 1096-0384 0003-9861 |
Palabras clave: | Doxorubicin Reactive oxygen species GKT137831 Ca2þ transporters NADPH oxidase Cardiotoxicity |
Resumen: | In atrial-derived HL-1 cells, ryanodine receptor and Naþ/Ca2þ-exchanger were altered early by 5 mM doxorubicin. The observed effects were an increase of cytosolic Ca2þ at rest, ensuing ryanodine receptor phosphorylation, and the slowing of Ca2þ transient decay after caffeine addition. Doxorubicin triggered a linear rise of reactive oxygen species (ROS) with no early effect on mitochondrial inner membrane potential. Doxorubicin and ROS were both detected in mitochondria by colocalization with fluorescence probes and doxorubicin-induced ROS was totally blocked by mitoTEMPO. The NADPH oxidase activity in the mitochondrial fraction was sensitive to inhibition by GKT137831, and doxorubicin-induced ROS decreased gradually as the GKT137831 concentration added in preincubation was increased. When doxorubicin-induced ROS was prevented by GKT137831, the kinetic response revealed a permanent degree of protection that was consistent with mitochondrial NADPH oxidase inhibition. In contrast, the ROS induction by doxorubicin after melatonin preincubation was totally eliminated at first but the effect was completely reversed with time. Limiting the source of ROS production is a better alternative for dealing with oxidative damage than using ROS scavengers. The short-term effect of doxorubicin on Ca2þ transporters involved in myocardiac contractility was dependent on oxidative damage, and so the impairment was subsequent to ROS production. |
Autor/es principal/es: | Asensio Lopez, Maria del Carmen Soler, Fernando Sanchez Mas, Jesus Pascual Figal, Domingo A. Fernandez Belda, Francisco Lax Pérez, Antonio Manuel |
Facultad/Departamentos/Servicios: | Facultades, Departamentos, Servicios y Escuelas::Departamentos de la UMU::Medicina |
URI: | http://hdl.handle.net/10201/137568 |
DOI: | 10.1016/j.abb.2016.02.021 |
Tipo de documento: | info:eu-repo/semantics/article |
Número páginas / Extensión: | 11 |
Derechos: | info:eu-repo/semantics/openAccess Attribution-NonCommercial-NoDerivatives 4.0 Internacional |
Descripción: | ©2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Accepted version of a Published Work that appeared in final form in Archives of Biochemistry and Biophysics. To access the final edited and published work see https://doi.org/10.1016/j.abb.2016.02.021 |
Aparece en las colecciones: | Artículos: Medicina |
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