title: Early phosphatidylinositol 3-kinase/Akt pathway activation limits poliovirus-induced JNK-mediated cell death.
abstract: Poliovirus (PV)-induced apoptosis seems to play a major role in tissue injury in the central nervous system (CNS). We have previously shown that this process involves PV-induced Bax-dependent mitochondrial dysfunction mediated by early JNK activation in IMR5 neuroblastoma cells. We showed here that PV simultaneously activates the phosphatidylinositol 3-kinase (PI3K)/Akt survival signaling pathway in these cells, limiting the extent of JNK activation and thereby cell death. JNK inhibition is associated with PI3K-dependent negative regulation of the apoptosis signal-regulating kinase 1, which acts upstream from JNK in PV-infected IMR5 cells. In poliomyelitis, this survival pathway may limit the spread of PV-induced damage in the CNS.
authors.affiliation: Biologie des Virus Entériques, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris cedex 15, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Autret
authors.forename: Sandra
authors.initials: S
authors.lastname: Martin-Latil
authors.forename: Cynthia
authors.initials: C
authors.lastname: Brisac
authors.forename: Laurence
authors.initials: L
authors.lastname: Mousson
authors.forename: Florence
authors.initials: F
authors.lastname: Colbère-Garapin
authors.forename: Bruno
authors.initials: B
authors.lastname: Blondel
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors; D048848:MAP Kinase Kinase Kinase 5 / Q000037:antagonists & inhibitors; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D017955:Poliovirus / Q000502:physiology*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D048848:MAP Kinase Kinase Kinase 5; D048670:MAP Kinase Kinase 4