Lipid peroxidation and superoxide dismutase-1 and glutathione peroxidase activities in trisomy 16 fetal mice and human trisomy 21 fibroblasts.
An increase in lipid peroxidation has been reported in fetal human trisomy 21 brains. To determine whether this change can be regarded as a consequence of the increase in soluble Cu, Zn-superoxide dismutase (SOD-1) activity caused by the trisomy, we have made use of the trisomy 16 mouse, a model for human trisomy 21. Lipid peroxidation, as malonaldehyde, and the activities of SOD-1 and glutathione peroxidase were studied in diploid and trisomy 16 mouse fetuses and fetal brains and, for comparison, in diploid and trisomy 21 human fibroblasts. SOD-1 activity in diploid mouse brain increased during fetal and postnatal development, but glutathione peroxidase activity was unchanged. Mean SOD-1 activity was almost exactly 50% increased in trisomy 16 fetuses and fetal brains and in human trisomy 21 fibroblasts, confirming the gene dosage effect in both species. The SOD-1 activity in the trisomic fetuses was correlated with that in their matched diploid littermates, suggesting that factors other than the gene dosage also determine activity. Mean glutathione peroxidase activity was not increased in trisomy 16 fetuses or brains and only slightly increased in human trisomy 21 fibroblasts. Mean lipid peroxidation was decreased in fetal trisomy 16 brains but was increased in human trisomy 21 fibroblasts. These results do not lend support to the notion that increased SOD-1 activity is developmentally deleterious and necessarily increases lipid peroxidation and, secondarily, the activity of glutathione peroxidase. The difference between the human and mouse data concerning lipid peroxidation in trisomic brains may be related to structural differences in the lipids which provide the substrate for lipid peroxidation.
D000818:Animals; D001921:Brain / Q000196:embryology / Q000201:enzymology; D002885:Chromosomes, Human, Pair 16; D004314:Down Syndrome / Q000201:enzymology*; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006801:Humans; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D051379:Mice; D011247:Pregnancy; D013482:Superoxide Dismutase / Q000378:metabolism*; D014314:Trisomy
D008054:Lipid Peroxides; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase