Upregulation of Connexin 43 Expression Via C-Jun N-Terminal Kinase Signaling in Prion Disease
| Autor: | Geon-Hwi Lee, Byungki Jang, Jeong-Ho Park, Yong-Sun Kim, Eun-Kyoung Choi, Hee-Jun Kim, Yong-Chul Jeon, Hong-Seok Choi, Richard I. Carp |
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| Rok vydání: | 2016 |
| Předmět: |
Cell signaling
PrPSc Proteins MAP Kinase Signaling System Connexin Scrapie Biology Downregulation and upregulation Animals RNA Messenger Cells Cultured Mice Knockout Mesocricetus General Neuroscience Cell Membrane c-jun JNK Mitogen-Activated Protein Kinases Brain General Medicine Up-Regulation Cell biology Mice Inbred C57BL Disease Models Animal Psychiatry and Mental health Clinical Psychology Connexin 43 cardiovascular system sense organs biological phenomena cell phenomena and immunity Geriatrics and Gerontology Signal transduction Cell activation |
| Zdroj: | Journal of Alzheimer's Disease. 49:1005-1019 |
| ISSN: | 1875-8908 1387-2877 |
| DOI: | 10.3233/jad-150283 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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