Induction of chemokines, MCP-1, and KC in the mutant huntingtin expressing neuronal cells because of proteasomal dysfunction
Autor: | Anand Goswami, Nihar Ranjan Jana, Sudheendra N.R. Rao, Nobuyuki Nukina, Amit Mishra, Doronala Narender, Swetha K. Godavarthi |
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Rok vydání: | 2009 |
Předmět: |
Genetically modified mouse
Proteasome Endopeptidase Complex congenital hereditary and neonatal diseases and abnormalities Chemokine Huntingtin Immunoblotting Mutant Mice Transgenic Nerve Tissue Proteins Transfection Biochemistry Mice Viral Proteins Cellular and Molecular Neuroscience Huntington's disease Genes Reporter mental disorders medicine Huntingtin Protein Animals Humans Cells Cultured Chemokine CCL2 Neurons biology Reverse Transcriptase Polymerase Chain Reaction Interleukin-8 NF-kappa B Nuclear Proteins medicine.disease Immunohistochemistry Molecular biology nervous system Proteasome Chemokines CC Mutation biology.protein Mitogen-Activated Protein Kinases |
Zdroj: | Journal of Neurochemistry. 108:787-795 |
ISSN: | 1471-4159 0022-3042 |
Popis: | Huntington's disease is a hereditary neurodegenerative disorder caused by an aberrant polyglutamine expansion in the amino terminus of the huntingtin protein. The resultant mutant huntingtin form aggregates in neurons and causes neuronal dysfunction and degeneration in many ways including transcriptional dysregulation. Here, we report that the expression of mutant huntingtin in the mouse neuroblastoma cell results in massive transcriptional induction of several chemokines including monocyte chemoattractant protein-1 (MCP-1) and murine chemokine (KC). The mutant huntingtin expressing cells also exhibit proteasomal dysfunction and down-regulation of NF-kappaB activity in a time-dependent manner and both these phenomena regulate the expression of MCP-1 and KC. The expression of MCP-1 and KC are increased in the mutant huntingtin expressing cells in response to mild proteasome inhibition. However, the expression of MCP-1 and KC and proteasome activity are not altered and inflammation is rarely observed in the brain of 12-week-old Huntington's disease transgenic mice in comparison with their age-matched controls. Our result suggests that the mutant huntingtin-induced proteasomal dysfunction can up-regulate the expression of MCP-1 and KC in the neuronal cells and therefore might trigger the inflammation process. |
Databáze: | OpenAIRE |
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