Hypothalamic digoxin-mediated model for trisomy 21.
The isoprenoid pathway related cascade was assessed in trisomy 21. Membrane Na+, K(+)-ATPase activity, serum magnesium, and ubiquinone were decreased while hydroxy methyl glutaryl CoA (HMG) coenzyme A (CoA) reductase activity, serum digoxin, and dolichol levels were increased in trisomy 21. There were increased levels of tryptophan catabolites--nicotine, strychnine, quinolinic acid, and serotonin--and decreased levels of tyrosine catabolites--dopamine, noradrenaline, and morphine in trisomy 21. There was an increase in dolichol levels, carbohydrate residues of glycoproteins, glycolipids, total/individual glycosaminoglycan (GAG) fractions, and lysosomal enzymes in trisomy 21. Reduced levels of ubiquinone, reduced glutathione, and free radical scavenging enzymes as well as increased lipid peroxidation products and nitric oxide were noticed in trisomy 21. Hypothalamic digoxin and a disordered isoprenoid pathway are important in the pathogenesis of trisomy 21.
Kurup
Ravi Kumar
RK
Department of Neurology, Medical College, Trivandrum, Kerala, India.
Kurup
Parameswara Achutha
PA
D000470:Alkaloids / Q000097:blood; D000818:Animals; D004077:Digoxin / Q000097:blood*; D004286:Dolichols / Q000097:blood; D004314:Down Syndrome / Q000097:blood* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000737:chemistry / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006903:Hydroxymethylglutaryl CoA Reductases / Q000097:blood; D007031:Hypothalamus / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013729:Terpenes / Q000378:metabolism; D014451:Ubiquinone / Q000097:blood
D000470:Alkaloids; D004286:Dolichols; D004791:Enzyme Inhibitors; D005609:Free Radicals; D013729:Terpenes; D014451:Ubiquinone; D004077:Digoxin; D006903:Hydroxymethylglutaryl CoA Reductases; D000254:Sodium-Potassium-Exchanging ATPase