SEARCH

SEARCH BY CITATION

Keywords:

  • Parkinson's disease;
  • Mitochondria;
  • Calcium

Abstract

  1. Top of page
  2. Abstract

Abstract: Parkinson's disease may be linked to defects in mitochondrial function. Mitochondrially transformed cells (cybrids) were created from Parkinson's disease patients or disease-free controls. Parkinson's disease cybrids had 26% less complex I activity, but maintained comparable basal calcium and energy levels. Parkinson's disease cybrids recovered from a carbachol-induced increase in cytosolic calcium 53% more slowly than controls even with lanthanum and thapsigargin blockade. Inhibition of complex I with the Parkinson's disease-inducing metabolite 1-methyl-4-phenylpyridinium (MPP+) similarly reduced the rate of recovery after carbachol. This MPP+-induced reduction in recovery rates was much more pronounced in control cybrids than in Parkinson's disease cybrids. Parkinson's disease cybrids had less carbonyl cyanide m-chlorophenylhydrazone-releasable calcium. Bypassing complex I with succinate partially restored Parkinson's disease cybrid, and MPP+ suppressed control cybrid recovery rates. The subtle alteration in calcium homeostasis of Parkinson's disease cybrids may reflect an increased susceptibility to cell death under circumstances not ordinarily toxic.

Abbreviations used: ANOVA, analysis of variance; CCCP, carbonyl cyanide m-chlorophenylhydrazone; ETC, electron transport chain; F, fluorescence intensity; HKRB, HEPES/Krebs/Ringer buffer; InsP3, inositol 1,4,5-trisphosphate; MPP+, 1-methyl-4-phenylpyridinium; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; mtDNA, mitochondrial DNA; PD, Parkinson's disease; PLSD, protected least significant difference.