Increased apoptosis of Huntington disease lymphoblasts associated with repeat length-dependent mitochondrial depolarization

Nat Med. 1999 Oct;5(10):1194-8. doi: 10.1038/13518.

Abstract

Huntington disease (HD) is a genetically dominant condition caused by expanded CAG repeats coding for glutamine in the HD gene product huntingtin. Although HD symptoms reflect preferential neuronal death in specific brain regions, huntingtin is expressed in almost all tissues, so abnormalities outside the brain might be expected. Although involvement of nuclei and mitochondria in HD pathophysiology has been suggested, specific intracellular defects that might elicit cell death have been unclear. Mitochondria dysfunction is reported in HD brains; mitochondria are organelles that regulates apoptotic cell death. We now report that lymphoblasts derived from HD patients showed increased stress-induced apoptotic cell death associated with caspase-3 activation. When subjected to stress, HD lymphoblasts also manifested a considerable increase in mitochondrial depolarization correlated with increased glutamine repeats.

MeSH terms

  • Adolescent
  • Adult
  • Apoptosis*
  • Caspase 3
  • Caspases / metabolism
  • Cyanides / pharmacology
  • Enzyme Activation
  • Glutamine / genetics
  • Hematopoietic Stem Cells / pathology*
  • Humans
  • Huntington Disease / etiology
  • Huntington Disease / genetics*
  • Lymphocytes / pathology*
  • Mitochondria / physiology*
  • Staurosporine / pharmacology
  • Trinucleotide Repeats*

Substances

  • Cyanides
  • Glutamine
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Staurosporine