Study of mitochondrial enzymes: cytochrome c oxidoreductase [complex III], and cytochrome oxidase [complex IV] with copper-zinc containing superoxide dismutase [SOD1] in children with down syndrome

ABSTRACT

Neither the pathogenesis nor the etiology of Down Syndrome [DS] are clearly understood. There is no evidence however that individual loci are responsible, or that the oxidative damage in DS could be solely explained by a gene dosage effect. Oxidative stress resulting from mitochondrial dysfunction may implicate the role of mitochondrial genome in DS pathogenesis and etiology. Moreover, the early Alzheimer's disease [AD] in DS is attributed to defective mitochondrial enzymes. The aim of the present work was to estimate the activity of mitochondrial electron transport enzymes cytochrome c oxidoreductase [complex III], cytochrome c-oxidase [complex IV] and copper-zinc containing superoxide dismutase [SOD-1] enzymes in children with Down syndrome and compare them with those of the normal children. The study was carried out on 30 Down syndrome children diagnosed by karyotyping and typical healthy children served as controls. Estimation of complex III, complex IV and Cu-Zn containing dismutase enzymes activities were done using spectrophotometeric methods. The results showed that there was a significant increase in the activity of SOD-1 in Down syndrome children compared to normal children with significant increase in DS children children above 5 years and controls. As regards complex III and complex IV results, there was significant decrease in their activities compared to controls. DS children > 5 years had significantly lower complex III activity than controls. DS children with epilepsy had significantly higher mean activity of SOD-1 than DS children without epilepsy. Both SOD-1 and complex III had significant inverse correlation with head circumference and there was no correlation between the three studied enzymes and the presence of congenital heart defects. Deficiency of the studied mitochondrial respiratory enzymes associated with increase in the activity of superoxide dismutase are a consequence of a generalized mitochondrial disturbance which may lie behind some pathogenetic aspects of Down syndrome and could contribute to impairment of energy metabolism and neurodegeneration, observed in DS