Mitochondrial and bioenergetic dysfunction in human hepatic cells infected with dengue 2 virus
Mitochondrial and bioenergetic dysfunction in human hepatic cells infected with dengue 2 virus
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DOI：
10.1016/j.bbadis.2007.08.003
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发表时间：
2007-10-01
影响因子：
6.2
通讯作者：
Da Poian, Andrea T.
中科院分区：
文献类型：
--
作者：
El-Bacha, Tatiana;Midlej, Victor;Da Poian, Andrea T.
登革热病毒感染影响着全世界数百万人。尽管登革热病毒引起的疾病的临床表现是已知的，但涉及细胞功能恶化的病理生理机制尚不清楚。在这项研究中，我们首次评估了登革热病毒诱导的细胞死亡与人类肝癌细胞系 HepG2 中线粒体功能之间的关联。登革热病毒感染促进了线粒体生物能学的变化，例如细胞呼吸的增加和 A Delta psi(m) 的减少。这些改变最终导致受病毒感染细胞的 ATP 含量减少 20%，能量消耗减少 15%。此外，病毒感染的细胞表现出多种超微结构改变，包括线粒体肿胀和细胞凋亡过程中典型的其他形态变化。线粒体生理学和能量稳态的改变发生在细胞死亡之前。这些结果表明，感染登革热病毒的HepG2细胞处于代谢应激状态，线粒体功能障碍和细胞ATP平衡的改变可能与登革热病毒感染的发病机制有关。 (C) 2007 Elsevier B.V. 保留所有权利。
Dengue virus infection affects millions of people all over the world. Although the clinical manifestations of dengue virus-induced diseases are known, the physiopathological mechanisms involved in deteriorating cellular function are not yet understood. In this study we evaluated for the first time the associations between dengue virus-induced cell death and mitochondrial function in HepG2, a human hepatoma cell line. Dengue virus infection promoted changes in mitochondrial bioenergetics, such as an increase in cellular respiration and a decrease in A Delta psi(m). These alterations culminated in a 20% decrease in ATP content and a 15% decrease in the energy charge of virus-infected cells. Additionally, virus-infected cells showed several ultrastructural alterations, including mitochondria swelling and other morphological changes typical of the apoptotic process. The alterations in mitochondrial physiology and energy homeostasis preceded cell death. These results indicate that HepG2 cells infected with dengue virus are under metabolic stress and that mitochondrial dysfunction and alterations in cellular ATP balance may be related to the pathogenesis of dengue virus infection. (C) 2007 Elsevier B.V. All rights reserved.