title: Avian reovirus S1133-induced apoptosis is associated with Bip/GRP79-mediated Bim translocation to the endoplasmic reticulum.
abstract: In this study the mechanism of avian reovirus (ARV) S1133-induced pathogenesis was investigated, with a focus on the contribution of ER stress to apoptosis. Our results showed that upregulation of the ER stress response protein, as well as caspase-3 activation, occurred in ARV S1133-infected cultured cells and in SPF White Leghorn chicks organs. Upon infection, Bim was translocated specifically to the ER, but not mitochondria, in the middle to late infectious stages. In addition, ARV S1133 induced JNK phosphorylation and promoted JNK-Bim complex formation, which correlated with the Bim translocation and apoptosis induction that was observed at the same time point. Knockdown of BiP/GRP78 by siRNA and inhibition of BiP/GRP78 using EGCG both abolished the formation of the JNK-Bim complex, caspase-3 activation, and subsequent apoptosis induction by ARV S1133 efficiently. These results suggest that BiP/GRP78 played critical roles and works upstream of JNK-Bim in response to the ARV S1133-mediated apoptosis process.
authors.affiliation: Department of Biological Science and Technology, National Pingtung University of Science and Technology, 1, Shuefu Rd., Neipu, 91201, Pingtung, Taiwan.
authors.forename: Ping-Yuan
authors.initials: PY
authors.lastname: Lin
authors.forename: Hung-Jen
authors.initials: HJ
authors.lastname: Liu
authors.forename: Ching-Dong
authors.initials: CD
authors.lastname: Chang
authors.forename: Yo-Chia
authors.initials: YC
authors.lastname: Chen
authors.forename: Chi-I
authors.initials: CI
authors.lastname: Chang
authors.forename: Wen-Ling
authors.initials: WL
authors.lastname: Shih
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D000072224:Bcl-2-Like Protein 11; D053148:Caspase 3 / Q000378:metabolism; D002645:Chickens; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D030101:Orthoreovirus, Avian / Q000235:genetics / Q000502:physiology*; D011201:Poultry Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012088:Reoviridae Infections / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000662:veterinary* / Q000821:virology; D015398:Signal Transduction
chemical_list: D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D053148:Caspase 3