EV71 infection induces cell apoptosis through ROS generation and SIRT1 activation. Issue 10 (2nd January 2020)

• Record Type: Journal Article
• Authors: Li, Hongyan; Bai, Zhenzi; Li, Chenghua; Sheng, Chuanlun; Zhao, Xiaonan
• Is Part Of: Journal of cellular biochemistry. Volume 121:Issue 10(2020)
• Page Start: 4321
• Page End: 4331
• Publication Date: 2020-01-02
• Subjects: apoptosis -- EV71 -- inflammation -- ROS -- SIRT1; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.29628
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: Several studies have substantiated the correlation between reactive oxygen species (ROS) and Sirtuin 1 (SIRT1). Normally, enterovirus 71 (EV71) is associated with severe clinical manifestations and death. However, the effect of EV71 on the induction of cellular death and the interplay between ROS/SIRT1 in cell death has not been confirmed yet. In the current study, an increase in the number of apoptotic cells was observed as soon as the EV71 infection was initiated in cells and mice. Furthermore, EV71 infection also promoted a rise in the levels of three commonly known proinflammatory cytokines, interleukin 1β (IL‐1β), IL‐6, and tumor necrosis factor‐α. During EV71‐induced apoptosis in the different cell lines, ROS generation and SIRT1 downregulation were observed. Further investigations showed that the administration of ROS inhibitor, N‐acetyl‐ l ‐cysteine (NAC), reduced the level of apoptosis and inflammation, reduced EV71 propagation, and increased SIRT1 expression in EV71‐infected cells. In addition, combined administration of NAC and EX527 (SIRT1 inhibitor) restored apoptosis in the EV71‐infected cells, which was reduced due to NAC. This data demonstrated that ROS generation is positively associated with EV71‐induced apoptosis and inflammation, while this effect could be reversed by SIRT1 inhibition. Collectively, we have shown that EV71 induces apoptosis and inflammation by promoting ROS generation and reducing SIRT1 expression. Abstract : In this study, we have revealed how the expression of the main mediating factors associated with apoptosis (Sirtuin 1 [SIRT1] and reactive oxygen species [ROS]) were affected by the involvement of enterovirus 71 (EV71) in various cell lines as well as mice. We found that a critical role of upregulated ROS and downregulated SIRT1 on EV71 proliferation in infected cells. Knockdown or knockout of SIRT1 in mice might be a useful tool to study the precise role of SIRT1.