Inhibition of calpain-mediated BAX cleavage attenuates Japanese encephalitis virus-induced apoptosis in SH-SY5Y neuroblastoma cells

Information from the abstract

BACKGROUND: Japanese encephalitis virus (JEV) is an arbovirus which is the most common virus in the genus Orthoflavivirus that causes significant viral encephalitis with a high fatality rate and is distributed throughout Asian countries. JEV infection induces brain tissue disease characterized by neuronal death. We previously demonstrated that JEV elevates the formation of an N-terminal truncated version of BAX (p18 BAX), triggering mitochondria-mediated apoptosis. However, the mechanisms by which virus-host interactions induce the generation of p18 BAX during JEV infection are unclear. METHODS: The present study aims to investigate the underlying mechanism by which JEV-induced cell apoptosis is mediated by the activation of calpain-induced proteolytic cleavage of BAX. Calpeptin, a calpain inhibitor, was used to evaluate the effect on calpain activity, cell viability, and apoptotic molecules expression in JEV-infected neuroblastoma SH-SY5Y cells. RESULTS: Our data showed that JEV infection resulted in the activation of the calpain-mediated apoptosis pathway, as evidenced by increased calpain activation and p18 BAX generation. The translocation of p18 BAX to the mitochondria results in cytochrome c release and increased of caspase-3 activity, resulting in an increase of cleaved PARP expression, which induced neuronal apoptosis. Inhibiting calpain activity by calpeptin attenuated all these effects. CONCLUSIONS: Our results reveal that JEV induces neuronal cell apoptosis by activating calpain-mediated cleavage of BAX. These findings provide a novel insight into JEV-caused encephalitis and suggest that calpain inhibition may represent a potential therapeutic strategy.

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Related topics: Mosquito-borne diseases and control · Calpain Protease Function and Regulation · Endoplasmic Reticulum Stress and Disease