Mitochondrial translocator protein (TSPO) ligands prevent doxorubicin-induced mechanical dysfunction and cell death in isolated cardiomyocytes.

Alexandra d'Anglemont De Tassigny; Rana Assaly; Sophie Schaller; Rebecca Pruss; Alain Berdeaux; Didier Morin

doi:10.1016/j.mito.2013.10.001

Mitochondrial translocator protein (TSPO) ligands prevent doxorubicin-induced mechanical dysfunction and cell death in isolated cardiomyocytes.

Alexandra d'Anglemont De Tassigny ^{1, 2} Rana Assaly ¹ Sophie Schaller ³ Rebecca Pruss ^{1, 3} Alain Berdeaux ¹ Didier Morin ^{1, *}

* Auteur correspondant

1 IMRB - Institut Mondor de Recherche Biomédicale

2 Institut Supérieur de BioSciences

3 Trophos S.A.

Abstract : Contractile dysfunction and subsequent development of cardiomyopathies are well known limiting factors in the treatment of cancer with doxorubicin and have been linked to mitochondrial dysfunction. Here, using adult isolated paced cardiomyocytes, we have demonstrated that ligands of translocator protein (TSPO) 4'-chlorodiazepam and TRO40303 prevented the doxorubicin-induced alterations in contractility and improved cardiomyocyte viability. This cardioprotective effect was closely associated with both a potent reduction in reactive oxygen species production and inhibition of mitochondrial permeability transition pore opening. Thus, preventive administration of TSPO ligands may represent a novel pharmacological strategy to protect the heart during doxorubicin treatment.

Keywords : cardiomyocytes doxorubicin mitochondria permeability transition pore ROS TSPO ligands

Type de document :

Article dans une revue

Mitochondrion, Elsevier, 2013, 13 (6), pp.688-97. 〈10.1016/j.mito.2013.10.001〉

Domaine :

Sciences du Vivant [q-bio] / Biochimie, Biologie Moléculaire

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http://www.hal.inserm.fr/inserm-00920557
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Dernière modification le : mercredi 27 janvier 2016 - 17:38:07
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Mitochondrial translocator protein (TSPO) ligands prevent doxorubicin-induced mechanical dysfunction and cell death in isolated cardiomyocytes.

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Mitochondrial translocator protein (TSPO) ligands prevent doxorubicin-induced mechanical dysfunction and cell death in isolated cardiomyocytes.

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