Truncated peroxisome proliferator-activated receptor-γ coactivator 1α splice variant is severely altered in Huntington's disease. Academic Article uri icon

Overview

MeSH

  • Adipose Tissue, Brown
  • Aged
  • Animals
  • Blotting, Western
  • Brain Chemistry
  • Cells, Cultured
  • Chromatography, High Pressure Liquid
  • Cold Temperature
  • Corpus Striatum
  • Cyclic AMP
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Transgenic
  • Middle Aged
  • Mitochondria
  • Mutation
  • Myoblasts
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Protein Isoforms
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation

MeSH Major

  • Heat-Shock Proteins
  • Huntington Disease
  • Transcription Factors

abstract

  • Reduced peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α) gene expression has been observed in striatal cell lines, transgenic mouse models of Huntington's disease (HD), and brain tissue from HD patients. As this protein is a key transcription regulator of the expression of many mitochondrial proteins, these observations strongly support the role of aberrant mitochondrial function in the pathogenesis of HD. The PGC1α protein undergoes posttranslational modifications that affect its transcriptional activity. The N-truncated splice variant of PGC1α (NT-PGC1α) is produced in tissues, but the role of truncated splice variants of PGC1α in HD and in the regulation of mitochondrial gene expression has not been elucidated. To examine the expression and modulation of expression of NT-PGC1α levels in HD. We found that the NT-PGC1α protein, a splice variant of ∼38 kDa, but not full-length PGC1α is severely and consistently altered in human HD brain, human HD myoblasts, mouse HD models, and HD striatal cells. NT-PGC1α levels were significantly upregulated in HD cells and mouse brown fat by physiologically relevant stimuli that are known to upregulate PGC1α gene expression. This resulted in an increase in mitochondrial gene expression and cytochrome c content. Our data suggest that NT-PGC1α is an important component of the PGC1α transcriptional network, which plays a significant role in the pathogenesis of HD. Copyright © 2011 S. Karger AG, Basel.

publication date

  • 2011

has subject area

  • Adipose Tissue, Brown
  • Aged
  • Animals
  • Blotting, Western
  • Brain Chemistry
  • Cells, Cultured
  • Chromatography, High Pressure Liquid
  • Cold Temperature
  • Corpus Striatum
  • Cyclic AMP
  • Female
  • Heat-Shock Proteins
  • Humans
  • Huntington Disease
  • Male
  • Mice
  • Mice, Transgenic
  • Middle Aged
  • Mitochondria
  • Mutation
  • Myoblasts
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Protein Isoforms
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors
  • Up-Regulation

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3186722

Digital Object Identifier (DOI)

  • 10.1159/000327910

PubMed ID

  • 21757867

Additional Document Info

start page

  • 496

end page

  • 503

volume

  • 8

number

  • 6