Giuseppe
Emeritus
The PI3K/Akt pathway inhibits influenza A virus-induced Bax-mediated apoptosis by negatively regulating the JNK pathway via ASK1. (J Gen Virol., abstract, edited)
4. J Gen Virol. 2010 Feb 3. [Epub ahead of print]
The PI3K/Akt pathway inhibits influenza A virus-induced Bax-mediated apoptosis by negatively regulating the JNK pathway via ASK1.
Lu X, Masic A, Li Y, Shin Y, Liu Q, Zhou Y. - Vaccine and Infectious Disease Organization, University of Saskatchewan;
We have previously reported that influenza A virus infection activates the PI3K/Akt pathway. In addition, we showed that the mutant influenza A virus PR8-SH3-mf-1, which is unable to activate the PI3K/Akt pathway, is more pro-apoptotic than the wild-type (WT) virus. However, the molecular pathways involved in regulating this process remain unknown. Here we report that although both the WT and PR8-SH3-mf-1 viruses induced apoptosis, the PR8-SH3-mf-1 virus consistently showed greater potential to induce mitochondrial membrane disruption, cytochrome c release, and translocation and conformational change of Bax than the WT virus. Furthermore, the PR8-SH3-mf-1 virus was unable to phosphorylate apoptosis signal-regulating kinase 1 (ASK1) but induced higher levels of JNK phosphorylation than the WT virus. Blocking JNK activity could inhibit virus-induced Bax activation and apoptosis. Our results reveal that during influenza A virus infection, the PI3K/Akt pathway negatively regulates the JNK pathway via ASK1, thereby inhibiting JNK-dependent, Bax-mediated apoptosis.
PMID: 20130137 [PubMed - as supplied by publisher]
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4. J Gen Virol. 2010 Feb 3. [Epub ahead of print]
The PI3K/Akt pathway inhibits influenza A virus-induced Bax-mediated apoptosis by negatively regulating the JNK pathway via ASK1.
Lu X, Masic A, Li Y, Shin Y, Liu Q, Zhou Y. - Vaccine and Infectious Disease Organization, University of Saskatchewan;
We have previously reported that influenza A virus infection activates the PI3K/Akt pathway. In addition, we showed that the mutant influenza A virus PR8-SH3-mf-1, which is unable to activate the PI3K/Akt pathway, is more pro-apoptotic than the wild-type (WT) virus. However, the molecular pathways involved in regulating this process remain unknown. Here we report that although both the WT and PR8-SH3-mf-1 viruses induced apoptosis, the PR8-SH3-mf-1 virus consistently showed greater potential to induce mitochondrial membrane disruption, cytochrome c release, and translocation and conformational change of Bax than the WT virus. Furthermore, the PR8-SH3-mf-1 virus was unable to phosphorylate apoptosis signal-regulating kinase 1 (ASK1) but induced higher levels of JNK phosphorylation than the WT virus. Blocking JNK activity could inhibit virus-induced Bax activation and apoptosis. Our results reveal that during influenza A virus infection, the PI3K/Akt pathway negatively regulates the JNK pathway via ASK1, thereby inhibiting JNK-dependent, Bax-mediated apoptosis.
PMID: 20130137 [PubMed - as supplied by publisher]
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