Effect of diphenyl diselenide, diphenyl ditelluride and ebselen on cerebral Na(+), K(+)-ATPase activity in rats.
In the present study, we investigated the in vitro effect of diphenyl ditelluride, diphenyl diselenide and ebselen on Na(+), K(+)-ATPase activity of rat brain. The results demonstrated that all compounds significantly inhibited (in the muM range) Na(+), K(+)-ATPase activity. Diphenyl ditelluride, at low concentrations, provoked an increase in Na(+), K(+)-ATPase activity. Dithiothreitol (DTT), at 3mM, protected the inhibition caused by diphenyl ditelluride, diphenyl diselenide and ebselen in Na(+), K(+)-ATPase activity. Post-incubation of diphenyl diselenide-treated homogenate with DTT completely recovered enzyme activity. DTT was able to recover the enzyme inhibition induced by 20muM of diphenyl ditelluride, but was partially able to recover inhibition induced by high concentrations of organotellurium compound. Conversely, DTT did not recover ebselen-induced Na(+), K(+)-ATPase inhibition. The mechanism of inhibition by diphenyl diselenide, diphenyl ditelluride and ebselen in Na(+), K(+)-ATPase activity revealed: decreased maximal velocity and K(m). Cerebral Na(+), K(+)-ATPase is a potential molecular target for the toxic effect of organochalcogens and the inhibition may occur through a change in the crucial thiol groups of this enzyme.
Borges
V C
VC
Departamento de Quimica, Centro de Ciencias Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.
Rocha
J B T
JB
Nogueira
C W
CW
D000818:Animals; D001393:Azoles / Q000633:toxicity; D001555:Benzene Derivatives / Q000633:toxicity; D001921:Brain / Q000187:drug effects* / Q000201:enzymology*; D004229:Dithiothreitol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004791:Enzyme Inhibitors / Q000633:toxicity*; D054833:Isoindoles; D008297:Male; D018696:Neuroprotective Agents / Q000633:toxicity; D009942:Organometallic Compounds / Q000633:toxicity; D016566:Organoselenium Compounds / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D001393:Azoles; D001555:Benzene Derivatives; D004791:Enzyme Inhibitors; D054833:Isoindoles; D018696:Neuroprotective Agents; D009942:Organometallic Compounds; D016566:Organoselenium Compounds; C434247:diphenylditelluride; C061132:diphenyldiselenide; C042986:ebselen; D000254:Sodium-Potassium-Exchanging ATPase; D004229:Dithiothreitol