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Early oxidative damage induced by doxorubicin: Source of production, protection by GKT137831 and effect on Ca(2+) transporters in HL-1 cardiomyocytes

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dc.contributor.authorAsensio Lopez, Maria del Carmen
dc.contributor.authorSanchez Mas, Jesus
dc.contributor.authorPascual Figal, Domingo A.
dc.contributor.authorFernandez Belda, Francisco
dc.contributor.authorLax Pérez, Antonio Manuel
dc.contributor.authorSoler Pardo, Fernando
dc.contributor.departmentMedicina
dc.date.accessioned2024-01-23T09:48:29Z
dc.date.available2024-01-23T09:48:29Z
dc.date.issued2016
dc.description©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.2016.02.021es
dc.description.abstractIn 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.es
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dc.identifier.citationArch Biochem Biophys. 2016 Mar 15:594:26-36.doi: 10.1016/j.abb.2016.02.021. Epub 2016 Feb 22.
dc.identifier.doi10.1016/j.abb.2016.02.021
dc.identifier.issn1096-0384
dc.identifier.issn0003-9861
dc.identifier.urihttp://hdl.handle.net/10201/137568
dc.languageenges
dc.relationThis study was supported in part by Grant FFIS/CM10/011 from Fundacion CajaMurcia, Murcia, Spaies
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectDoxorubicines
dc.subjectReactive oxygen specieses
dc.subjectGKT137831es
dc.subjectCa2þ transporterses
dc.subjectNADPH oxidasees
dc.subjectCardiotoxicityes
dc.titleEarly oxidative damage induced by doxorubicin: Source of production, protection by GKT137831 and effect on Ca(2+) transporters in HL-1 cardiomyocyteses
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
relation.isAuthorOfPublicationfb419085-b327-4302-860b-d0f7e5000ea9
relation.isAuthorOfPublication.latestForDiscoveryfb419085-b327-4302-860b-d0f7e5000ea9
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