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Induction of chemokines, MCP‐1, and KC in the mutant huntingtin expressing neuronal cells because of proteasomal dysfunction
Author(s) -
Godavarthi Swetha K.,
Narender Doronala,
Mishra Amit,
Goswami Anand,
Rao Sudheendra N. R.,
Nukiobuyuki,
Jaihar Ranjan
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05823.x
Subject(s) - huntingtin , chemokine , microbiology and biotechnology , huntingtin protein , mutant , biology , huntington's disease , proteasome , inflammation , mutant protein , immunology , gene , genetics , medicine , disease
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‐ κ B 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.