Striatal 19S Rpt6 deficit is related to alpha-synuclein accumulation in MPTP-treated mice

Biochem Biophys Res Commun. 2008 Nov 14;376(2):277-82. doi: 10.1016/j.bbrc.2008.08.142. Epub 2008 Sep 7.

Abstract

Striatal mitochondrial proteins were investigated using proteomics in the 1-methyl 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. Four proteins, 19S proteasome ATPase Rpt6 (19S Rpt6), Lectin-related nature killer cell receptor LY 49S, Zinc finger A20 domain containing 1, and the sodium channel-associated protein 1 isoform 2, were significantly decreased while alpha-synuclein was increased in MPTP-treated mice. The altered levels of 19S Rpt6 and alpha-synuclein were further verified by Western blot. Experiments using small interfering RNA (siRNA) showed that alpha-synuclein was increased by 50% in cultured striatal neurons when 19S Rpt6 was knocked down. Taken together, our results imply that a deficiency in 19S Rpt6 may be partially related to the MPTP-induced increase in alpha-synuclein in the striatum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology
  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Animals
  • Antigens, Ly / metabolism
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Corpus Striatum / pathology
  • Lectins, C-Type / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Neurotoxins / toxicity
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / genetics
  • Parkinson Disease, Secondary / metabolism*
  • Proteomics
  • RNA Interference
  • Receptors, NK Cell Lectin-Like
  • alpha-Synuclein / metabolism*

Substances

  • Antigens, Ly
  • Lectins, C-Type
  • Neurotoxins
  • Receptors, NK Cell Lectin-Like
  • alpha-Synuclein
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Adenosine Triphosphatases