Inhibition of rat brain Na+, K+-ATPase activity induced by homocysteine is probably mediated by oxidative stress.
The objective of the present study was to investigate the effects of preincubation of hippocampus homogenates in the presence of homocysteine or methionine on Na+, K+-ATPase and Mg2+-ATPase activities in synaptic membranes of rats. Homocysteine significantly inhibited Na+, K+-ATPase activity, whereas methionine had no effect. Mg2+-ATPase activity was not altered by the metabolites. We also evaluated the effect of incubating glutathione, cysteine, dithiothreitol, trolox, superoxide dismutase and GM1 ganglioside alone or incubation with homocysteine on Na+, K+-ATPase activity. Tested compounds did not alter Na+, K+-ATPase and Mg2+-ATPase activities, but except for trolox, prevented the inhibitory effect of homocysteine on Na+, K+-ATPase activity. These results suggest that inhibition of this enzyme activity by homocysteine is possibly mediated by free radicals and may contribute to the neurological dysfunction found in homocystinuric patients.
Streck
E L
EL
Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Zugno
A I
AI
Tagliari
B
B
Franzon
R
R
Wannmacher
C M
CM
Wajner
M
M
Wyse
A T
AT
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002839:Chromans / Q000494:pharmacology; D006624:Hippocampus / Q000201:enzymology*; D006710:Homocysteine / Q000494:pharmacology*; D007700:Kinetics; D008715:Methionine / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013482:Superoxide Dismutase / Q000494:pharmacology
D002839:Chromans; D006710:Homocysteine; D008715:Methionine; D013482:Superoxide Dismutase; D000254:Sodium-Potassium-Exchanging ATPase; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid