title: The activity of erythrocyte and brain Na+/K+ and Mg2+-ATPases in rats subjected to acute homocysteine and homocysteine thiolactone administration.
abstract: Hyperhomocysteinemia is associated with various pathologies including cardiovascular disease, stroke, and cognitive dysfunctions. Systemic administration of homocysteine can trigger seizures in animals, and patients with homocystinuria suffer from epileptic seizures. Available data suggest that homocysteine can be harmful to human cells because of its metabolic conversion to homocysteine thiolactone, a reactive thioester. A number of reports have demonstrated a reduction of Na+/K+-ATPase activity in cerebral ischemia, epilepsy and neurodegeneration possibly associated with excitotoxic mechanisms. The aim of this study was to examine the in vivo effects of D,L-homocysteine and D,L-homocysteine thiolactone on Na+/K+- and Mg2+-ATPase activities in erythrocyte (RBC), brain cortex, hippocampus, and brain stem of adult male rats. Our results demonstrate a moderate inhibition of rat hippocampal Na+/K+-ATPase activity by D,L-homocysteine, which however expressed no effect on the activity of this enzyme in the cortex and brain stem. In contrast, D,L-homocysteine thiolactone strongly inhibited Na+/K+-ATPase activity in cortex, hippocampus and brain stem of rats. RBC Na+/K+-ATPase and Mg2+-ATPase activities were not affected by D,L-homocysteine, while D,L-homocysteine thiolactone inhibited only Na+/K+-ATPase activity. This study results show that homocysteine thiolactone significantly inhibits Na+/K+-ATPase activity in the cortex, hippocampus, and brain stem, which may contribute at least in part to the understanding of excitotoxic and convulsive properties of this substance.
authors.affiliation: Laboratory of Neurophysiology, Institute of Medical Physiology, School of Medicine, University of Belgrade, Visegradska 26/II, 11000 Belgrade, Serbia.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Rasić-Marković
authors.forename: Olivera
authors.initials: O
authors.lastname: Stanojlović
authors.forename: Dragan
authors.initials: D
authors.lastname: Hrncić
authors.forename: Danijela
authors.initials: D
authors.lastname: Krstić
authors.forename: Mirjana
authors.initials: M
authors.lastname: Colović
authors.forename: Veselinka
authors.initials: V
authors.lastname: Susić
authors.forename: Tatjana
authors.initials: T
authors.lastname: Radosavljević
authors.forename: Dragan
authors.initials: D
authors.lastname: Djuric
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000378:metabolism; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism*; D004912:Erythrocytes / Q000201:enzymology* / Q000378:metabolism; D006710:Homocysteine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
chemical_list: D006710:Homocysteine; C007957:homocysteine thiolactone; D017301:Ca(2+) Mg(2+)-ATPase; D000254:Sodium-Potassium-Exchanging ATPase