Morphological alterations induced by doxorubicin on H9c2 myoblasts: nuclear, mitochondrial, and cytoskeletal targets
Morphological alterations induced by doxorubicin on H9c2 myoblasts: nuclear, mitochondrial, and cytoskeletal targets
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DOI：
10.1007/s10565-008-9070-1
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发表时间：
2009-06-01
影响因子：
6.1
通讯作者：
Wallace, Kendall B.
中科院分区：
文献类型：
--
作者：
Sardao, Vilma A.;Oliveira, Paulo J.;Wallace, Kendall B.
多柔比星（Dox）是一种非常有效的抗癌药物，用于治疗几种类型的癌症，尽管累积性心肌病会降低治疗指数。H9c2成肌细胞已被用作体外模型来研究Dox处理对心肌细胞诱导的生化改变。尽管已经发表了大量的工作，但关于Dox处理期间H9c2细胞的形态学改变的数据很少。本工作的目的是评估Dox诱导的H9c2成肌细胞的形态学改变，特别关注细胞核、线粒体和结构纤维蛋白。用低浓度的Dox处理H9c2细胞引起纤维结构蛋白的改变，包括核纤层和肌节心肌肌球蛋白，以及线粒体去极化和片段化，膜起泡伴细胞形状改变，以及磷脂酰丝氨酸外化。对于更高的Dox浓度，更深刻的变化是明显的，包括核肿胀与核膜结构的破坏，线粒体肿胀，和广泛的细胞质空泡化。所获得的结果表明，Dox引起H9c2细胞中线粒体、核和纤维蛋白结构的形态学改变，这取决于药物浓度。本研究获得的数据允许更好地表征Dox对H9c2成肌细胞的影响，用作研究Dox诱导的心脏毒性的模型。所获得的结果还提供了新的和以前未知的目标，可以有助于了解Dox心脏毒性的机制。
Doxorubicin (Dox) is a very potent antineoplastic agent used against several types of cancer, despite a cumulative cardiomyopathy that reduces the therapeutic index for treatment. H9c2 myoblast cells have been used as an in vitro model to study biochemical alterations induced by Dox treatment on cardiomyocyte cells. Despite the extensive work already published, few data are available regarding morphological alterations of H9c2 cells during Dox treatment. The purpose of the present work was to evaluate Dox-induced morphological alterations in H9c2 myoblasts, focusing especially on the nuclei, mitochondria, and structural fibrous proteins. Treatment of H9c2 cell with low concentrations of Dox causes alterations in fibrous structural proteins including the nuclear lamina and sarcomeric cardiac myosin, as well as mitochondrial depolarization and fragmentation, membrane blebbing with cell shape changes, and phosphatidylserine externalization. For higher Dox concentrations, more profound alterations are evident, including nuclear swelling with disruption of nuclear membrane structure, mitochondrial swelling, and extensive cytoplasm vacuolization. The results obtained indicate that Dox causes morphological alterations in mitochondrial, nuclear, and fibrous protein structures in H9c2 cells, which are dependent on the drug concentration. Data obtained with the present study allow for a better characterization of the effects of Dox on H9c2 myoblasts, used as a model to study Dox-induced cardiotoxicity. The results obtained also provide new and previously unknown targets that can contribute to understand the mechanisms involved in the cardiotoxicity of Dox.