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

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• 作者：Alex ; ra d'Anglemont de Tassigny ; Rana Assaly ; Sophie Schaller ; Rebecca M. Pruss ; Alain Berdeaux ; Didier Morin
• 关键词：BAPTA ; 1 ; 2-bis(o-aminophenoxy)ethane-N ; N ; N&prime ; N&prime ; -tetraacetic acid ; CoCl2 ; cobalt chloride ; CsA ; cyclosporin A ; DCF ; dichlorofluorescein ; DCFH-DA ; 2 ; 7-dichlorodihydrofluorescein-diacetate ; CDZ ; 4&prime ; -chlorodiazepam ; IMAC ; inner membrane anion channel ; mPTP ; mitochondrial permeability transition pore ; OH ; hydroxyl radical ; PI ; propidium iodide ; ROS ; reactive oxygen species ; TSPO ; translocator protein
• 刊名：Mitochondrion
• 出版年：November, 2013
• 年：2013
• 卷：13
• 期：6
• 页码：688-697
• 全文大小：2768 K

文摘

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鈥?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.