PMID- 19187096
OWN - NLM
STAT- MEDLINE
DCOM- 20090224
LR  - 20161125
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Linking)
VI  - 108
IP  - 3
DP  - 2009 Feb
TI  - Induction of chemokines, MCP-1, and KC in the mutant huntingtin expressing 
      neuronal cells because of proteasomal dysfunction.
PG  - 787-95
LID - 10.1111/j.1471-4159.2008.05823.x [doi]
AB  - 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.
FAU - Godavarthi, Swetha K
AU  - Godavarthi SK
AD  - Cellular and Molecular Neuroscience Laboratory, National Brain Research Centre, 
      Manesar, Gurgaon, India.
FAU - Narender, Doronala
AU  - Narender D
FAU - Mishra, Amit
AU  - Mishra A
FAU - Goswami, Anand
AU  - Goswami A
FAU - Rao, Sudheendra N R
AU  - Rao SN
FAU - Nukina, Nobuyuki
AU  - Nukina N
FAU - Jana, Nihar Ranjan
AU  - Jana NR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokines, CC)
RN  - 0 (HTT protein, human)
RN  - 0 (Huntingtin Protein)
RN  - 0 (Interleukin-8)
RN  - 0 (MCK-1 protein, Mouse cytomegalovirus 1)
RN  - 0 (NF-kappa B)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Viral Proteins)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CCL2/*biosynthesis/genetics
MH  - Chemokines, CC/*biosynthesis/genetics
MH  - Genes, Reporter/genetics
MH  - Humans
MH  - Huntingtin Protein
MH  - Immunoblotting
MH  - Immunohistochemistry
MH  - Interleukin-8/biosynthesis
MH  - Mice
MH  - Mice, Transgenic
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Mutation/physiology
MH  - NF-kappa B/genetics
MH  - Nerve Tissue Proteins/*genetics
MH  - Neurons/*metabolism
MH  - Nuclear Proteins/*genetics
MH  - Proteasome Endopeptidase Complex/*genetics/*physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transfection
MH  - Viral Proteins/*biosynthesis/genetics
EDAT- 2009/02/04 09:00
MHDA- 2009/02/25 09:00
CRDT- 2009/02/04 09:00
PHST- 2009/02/04 09:00 [entrez]
PHST- 2009/02/04 09:00 [pubmed]
PHST- 2009/02/25 09:00 [medline]
AID - JNC5823 [pii]
AID - 10.1111/j.1471-4159.2008.05823.x [doi]
PST - ppublish
SO  - J Neurochem. 2009 Feb;108(3):787-95. doi: 10.1111/j.1471-4159.2008.05823.x.