title: Activation of PI3K/Akt pathway limits JNK-mediated apoptosis during EV71 infection.
abstract: Apoptosis is frequently induced to inhibit virus replication during infection of Enterovirus 71 (EV71). On the contrary, anti-apoptotic pathway, such as PI3K/Akt pathway, is simultaneously exploited by EV71 to accomplish the viral life cycle. The relationship by which EV71-induced apoptosis and PI3K/Akt signaling pathway remains to be elucidated. In this study, we demonstrated that EV71 infection altered Bax conformation and triggered its redistribution from the cytosol to mitochondria in RD cells. Subsequently, cytochrome c was released from mitochondria to cytosol. We also found that c-Jun NH2-terminal kinase (JNK) was activated during EV71 infection. The JNK specific inhibitor significantly inhibited Bax activation and cytochrome c release, suggesting that EV71-induced apoptosis was involved into a JNK-dependent manner. Meanwhile, EV71-induced Akt phosphorylation involved a PI3K-dependent mechanism. Inhibition of the PI3K/Akt pathway enhanced JNK phosphorylation and the JNK-mediated apoptosis upon EV71 infection. Moreover, PI3K/Akt pathway phosphorylated apoptosis signal-regulating kinase 1 (ASK1) and negatively regulated the ASK1 activity. Knockdown of ASK1 significantly decreased JNK phosphorylation, which implied that ASK1 phosphorylation by Akt inhibited ASK1-mediated JNK activation. Collectively, these data reveal that activation of the PI3K/Akt pathway limits JNK-mediated apoptosis by phosphorylating and inactivating ASK1 during EV71 infection.
authors.affiliation: College of Life Science and Technology, HeiLongJiang BaYi Agricultural University, Daqing 163319, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: College of Life Science and Technology, HeiLongJiang BaYi Agricultural University, Daqing 163319, China.
authors.forename: Fengqi
authors.initials: F
authors.lastname: Li
authors.affiliation: College of Life Science and Technology, HeiLongJiang BaYi Agricultural University, Daqing 163319, China.
authors.forename: Ziye
authors.initials: Z
authors.lastname: Pan
authors.affiliation: College of Life Science and Technology, HeiLongJiang BaYi Agricultural University, Daqing 163319, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Wu
authors.affiliation: College of Life Science and Technology, HeiLongJiang BaYi Agricultural University, Daqing 163319, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Life Science and Technology, HeiLongJiang BaYi Agricultural University, Daqing 163319, China. Electronic address: cuiyudong@yahoo.com.
authors.forename: Yudong
authors.initials: Y
authors.lastname: Cui
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D029821:Enterovirus A, Human / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human; D048670:MAP Kinase Kinase 4
keywords: ASK1; Apoptosis; Enterovirus 71; JNK; PI3K/Akt pathway