title: Upregulation of Connexin 43 Expression Via C-Jun N-Terminal Kinase Signaling in Prion Disease.
abstract: Prion infection leads to neuronal cell death, glial cell activation, and the accumulation of misfolded prion proteins. However, the altered cellular environments in animals with prion diseases are poorly understood. In the central nervous system, cells connect the cytoplasm of adjacent cells via connexin (Cx)-assembled gap junction channels to allow the direct exchange of small molecules, including ions, neurotransmitters, and signaling molecules, which regulate the activities of the connected cells. Here, we investigate the role of Cx43 in the pathogenesis of prion diseases. Upregulated Cx43 expression, which was dependent on c-Jun N-Terminal Kinase (JNK)/c-Jun signaling cascades, was found in prion-affected brain tissues and hippocampal neuronal cells. Scrapie infection-induced Cx43 formed aggregated plaques within the cytoplasmic compartments at the cell-cell interfaces. The ethidium bromide (EtBr) uptake assay and scrape-loading dye transfer assay demonstrated that increased Cx43 has functional consequences for the activity of Cx43 hemichannels. Interestingly, blockade of PrPSc accumulation reduced Cx43 expression through the inhibition of JNK signaling, indicating that PrPSc accumulation may be directly involved in JNK activation-mediated Cx43 upregulation. Overall, our findings describe a scrapie infection-mediated novel regulatory signaling pathway of Cx43 expression and may suggest a role for Cx43 in the pathogenesis of prion diseases.
authors.affiliation: Ilsong Institute of Life Science, Hallym University, Anyang, Gyeonggi-do, Republic of Korea.|Department of Biomedical Gerontology, Graduate School of Hallym University, Chuncheon, Gangwon-do, Republic of Korea.
authors.forename: Geon-Hwi
authors.initials: GH
authors.lastname: Lee
authors.affiliation: Ilsong Institute of Life Science, Hallym University, Anyang, Gyeonggi-do, Republic of Korea.
authors.forename: Byungki
authors.initials: B
authors.lastname: Jang
authors.affiliation: Ilsong Institute of Life Science, Hallym University, Anyang, Gyeonggi-do, Republic of Korea.|Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do, Republic of Korea.
authors.forename: Hong-Seok
authors.initials: HS
authors.lastname: Choi
authors.affiliation: Ilsong Institute of Life Science, Hallym University, Anyang, Gyeonggi-do, Republic of Korea.
authors.forename: Hee-Jun
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Ilsong Institute of Life Science, Hallym University, Anyang, Gyeonggi-do, Republic of Korea.|Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do, Republic of Korea.
authors.forename: Jeong-Ho
authors.initials: JH
authors.lastname: Park
authors.affiliation: Ilsong Institute of Life Science, Hallym University, Anyang, Gyeonggi-do, Republic of Korea.
authors.forename: Yong-Chul
authors.initials: YC
authors.lastname: Jeon
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
authors.forename: Richard I
authors.initials: RI
authors.lastname: Carp
authors.affiliation: Ilsong Institute of Life Science, Hallym University, Anyang, Gyeonggi-do, Republic of Korea.|Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do, Republic of Korea.
authors.forename: Yong-Sun
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Ilsong Institute of Life Science, Hallym University, Anyang, Gyeonggi-do, Republic of Korea.|Department of Biomedical Gerontology, Graduate School of Hallym University, Chuncheon, Gangwon-do, Republic of Korea.
authors.forename: Eun-Kyoung
authors.initials: EK
authors.lastname: Choi
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D018031:Connexin 43 / Q000378:metabolism*; D004195:Disease Models, Animal; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008647:Mesocricetus; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018620:PrPSc Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012608:Scrapie / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D018031:Connexin 43; D018620:PrPSc Proteins; D012333:RNA, Messenger; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Connexin 43; JNK; gap junction; prion protein; scrapie