Evidence for increased mitochondrial superoxide production in Down syndrome

Respiring mitochondria represent the major source of superoxide production in most cells, and superoxide anions function as direct precursors of hydrogen peroxide formation within mitochondria. We use a lucigenen-derived chemiluminescence (LDCL) assay to test the hypothesis that intramitochondrial superoxide production is altered in young children with DS. We also measured the levels of two serum markers of lipid peroxidation, lipid peroxides (LOOH), and malondialdehyde as thiobarbituric acid reactive substances (TBARS), to determine if superoxide levels correlate with in vivo measures of lipid peroxidation. A three-group, cross-sectional design was utilized which allowed us to compare young children with DS to children with cognitive impairment (CI) of unknown etiology, and typically developing (Nl) children. Data was analyzed using Pearson's zero-order correlations and multivariate analysis of variance (MANOVA) with Bonferroni correction for multiple comparisons. DS subjects had significantly elevated LDCL signal compared to Nl subjects (p = .03), but did not differ significantly from CI subjects. This study provides new evidence regarding an important source of reactive oxygen species in trisomy 21. The role of the mitochondria in superoxide anion production and the mechanisms underlying its generation in DS deserves further study.