NDLI: Calcium flux and calpain-mediated activation of the apoptosis-inducing factor contribute to enterovirus 71-induced apoptosis.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lu, Jia-Rong Lu, Wen-Wen Lai, Jian-Zhong Tsai, Fu-Lian Wu, Szu-Hsien Lin, Cheng-Wen Kung, Szu-Hao
Description	Country affiliation: China Author Affiliation: Lu JR ( Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China.)
Abstract	Enterovirus 71 (EV71) is a causative agent of an array of childhood diseases with severe neurological manifestations implicated. EV71 infection is known to induce caspase-dependent apoptosis in cell cultures and animal models. However, whether an alternative apoptotic pathway independent of caspase activation can be triggered by EV71 infection has not been explored. In this study, we showed that calcium (Ca²âº)-activated calpains are capable of mediating caspase-independent pathway activation during EV71-induced apoptosis in HeLa cells. Results from subcellular fractionation analysis and confocal imaging indicated that during EV71 infection, apoptosis-inducing factor (AIF), a primary mediator of the caspase-independent pathway, became truncated and translocated from the mitochondrion to nucleus. This was accompanied by the release of cytochrome c, and sharply decreased mitochondrial membrane potential. AIF knockdown data indicated significant protection against apoptotic cell death, with greater protection provided by the addition of a pan-caspase inhibitor. The Ca²âº-dependent, calpain isoforms 1 and 2, but not cathepsins, were proven crucial for the altered AIF behaviour as studied by the pharmacological inhibitor and the knockdown approaches. We then analysed Ca²âº dynamics in the infected cells and found elevated levels of mitochondrial Ca²âº. Treatment with ruthenium red, a mitochondrial Ca²âº influx inhibitor, significantly blocked calpain activations and AIF cleavage. Our conclusion was that calpain activation via Ca²âº flux plays an essential role in eliciting an AIF-mediated, caspase-independent apoptotic pathway in EV71-infected cells. These findings should be useful for understanding the virus-induced cytopathology and the impact of Ca²âº homeostasis on EV71 infection.
File Format	HTM / HTML
ISSN	00221317
Issue Number	Pt 7
Volume Number	94
e-ISSN	14652099
Journal	Journal of General Virology
Language	English
Publisher	Microbiology Society
Publisher Date	2013-07-01
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Cell Line Research Support, Non-u.s. Gov't Calcium Enterovirus Infections Discipline Virology Apoptosis Inducing Factor Humans Calpain Enterovirus Metabolism Journal Article Virology Pathogenicity Cercopithecus Aethiops Mitochondria Animals Physiology Vero Cells Cell Nucleus Hela Cells Apoptosis
Content Type	Text
Resource Type	Article
Subject	Virology

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