Upregulation of Connexin 43 Expression Via C-Jun N-Terminal Kinase Signaling in Prion Disease

被引:5
|
作者
Lee, Geon-Hwi [1 ,2 ]
Jang, Byungki [1 ]
Choi, Hong-Seok [1 ,3 ]
Kim, Hee-Jun [1 ]
Park, Jeong-Ho [1 ,3 ]
Jeon, Yong-Chul [1 ]
Carp, Richard I. [4 ]
Kim, Yong-Sun [1 ,3 ]
Choi, Eun-Kyoung [1 ,2 ]
机构
[1] Hallym Univ, Ilsong Inst Life Sci, Anyang 431815, Gyeonggi Do, South Korea
[2] Hallym Univ, Grad Sch, Dept Biomed Gerontol, Chunchon, Gangwon Do, South Korea
[3] Hallym Univ, Coll Med, Dept Microbiol, Chunchon, Gangwon Do, South Korea
[4] New York State Inst Basic Res Dev Disabil, Staten Isl, NY 10314 USA
基金
新加坡国家研究基金会;
关键词
Connexin; 43; gap junction; JNK; prion protein; scrapie; GAP-JUNCTION HEMICHANNELS; NEURAL PROGENITOR CELLS; SPINAL-CORD-INJURY; GLUTAMATE RELEASE; INTERCELLULAR COMMUNICATION; CORTICAL ASTROCYTES; NEURONAL MIGRATION; NERVOUS-SYSTEM; BRAIN; PROTEIN;
D O I
10.3233/JAD-150283
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:1005 / 1019
页数:15
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