Cellular and Mitochondrial Glutathione Redox Imbalance in Lymphoblastoid Cells Derived From Children With Autism

FASEB J. 2009 Aug;23(8):2374-83. doi: 10.1096/fj.08-128926. Epub 2009 Mar 23.

Abstract

Research into the metabolic phenotype of autism has been relatively unexplored despite the fact that metabolic abnormalities have been implicated in the pathophysiology of several other neurobehavioral disorders. Plasma biomarkers of oxidative stress have been reported in autistic children; however, intracellular redox status has not yet been evaluated. Lymphoblastoid cells (LCLs) derived from autistic children and unaffected controls were used to assess relative concentrations of reduced glutathione (GSH) and oxidized disulfide glutathione (GSSG) in cell extracts and isolated mitochondria as a measure of intracellular redox capacity. The results indicated that the GSH/GSSG redox ratio was decreased and percentage oxidized glutathione increased in both cytosol and mitochondria in the autism LCLs. Exposure to oxidative stress via the sulfhydryl reagent thimerosal resulted in a greater decrease in the GSH/GSSG ratio and increase in free radical generation in autism compared to control cells. Acute exposure to physiological levels of nitric oxide decreased mitochondrial membrane potential to a greater extent in the autism LCLs, although GSH/GSSG and ATP concentrations were similarly decreased in both cell lines. These results suggest that the autism LCLs exhibit a reduced glutathione reserve capacity in both cytosol and mitochondria that may compromise antioxidant defense and detoxification capacity under prooxidant conditions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Adolescent
  • Adult
  • Autistic Disorder / etiology
  • Autistic Disorder / metabolism*
  • Case-Control Studies
  • Cell Line
  • Child
  • Cytosol / metabolism
  • Free Radicals / metabolism
  • Glutathione / metabolism*
  • Glutathione Disulfide / metabolism
  • Humans
  • Lymphocytes / drug effects
  • Lymphocytes / metabolism*
  • Male
  • Membrane Potential, Mitochondrial
  • Mitochondria / metabolism
  • Oxidative Stress / drug effects
  • S-Nitroso-N-Acetylpenicillamine / pharmacology
  • Thimerosal / pharmacology
  • Young Adult

Substances

  • Free Radicals
  • Thimerosal
  • S-Nitroso-N-Acetylpenicillamine
  • Adenosine Triphosphate
  • Glutathione
  • Glutathione Disulfide