Department of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.
Methods Mol Biol. 2022;2497:207-220. doi: 10.1007/978-1-0716-2309-1_13.
Doxorubicin (DOX)-induced cardiomyopathy constitutes dose-dependent cardiac toxicity, culminating in fatal heart failure progression. Cardiac toxicity limits effective and subsequent use of DOX in chemotherapy regimens in pediatric, adult, and recurrent cancer patients. DOX-induced profound alterations in mitochondrial morphology, dynamics, and defects in mitochondrial energy metabolism in the heart comprise key stressors in DOX-induced cardiotoxicity. Hence, the discovery of novel molecular targets and therapeutics to mitigate DOX-induced mitochondrial dysfunctions are imperative. Herein, we provided two laboratory protocols to monitor DOX-induced alterations in mitochondrial morphology and respiration in isolated primary neonatal rat cardiomyocytes. Neonatal rat cardiomyocytes are extensively used to monitor signaling mechanisms regulating cardiomyopathy in vitro. Therefore, these protocols will help researchers study the effects of novel pharmacological and genetic manipulations against DOX-induced alterations in mitochondrial morphology and energy metabolism in cardiomyocytes.
多柔比星（DOX）诱导的心肌病构成剂量依赖性心脏毒性，最终导致致命的心力衰竭进展。心脏毒性限制了 DOX 在儿科、成人和复发性癌症患者化疗方案中的有效和后续使用。DOX 诱导的线粒体形态、动力学的深刻改变以及心脏中线粒体能量代谢的缺陷，构成了 DOX 诱导的心脏毒性中的关键应激源。因此，发现新的分子靶点和治疗方法来减轻 DOX 诱导的线粒体功能障碍是至关重要的。在这里，我们提供了两种实验室方案来监测分离的原代新生大鼠心肌细胞中 DOX 诱导的线粒体形态和呼吸的改变。新生大鼠心肌细胞广泛用于体外监测调节心肌病的信号机制。因此，这些方案将帮助研究人员研究针对 DOX 诱导的心肌细胞中线粒体形态和能量代谢改变的新型药理学和遗传学操作的效果。
