Insights into the mechanism of Na+,K+-ATPase inhibition by 2-methoxy-3,8,9-trihydroxy coumestan.
The molecular mechanisms involved in Na+,K+-ATPase inhibition by 2-methoxy-3,8,9-trihydroxy coumestan were investigated. We show that this compound decreases the free sulfydryl groups present in the enzyme and that its inhibitory effect is prevented by dithiothreitol and other two sulfydryl containing reagents. We propose a redox cycle culminating with the irreversible oxidation of sulfydryl groups essential for the catalytic activity of this enzyme and of two other related P-type ATPases.
Pôças
Elisa S C
ES
Departamento de Farmacologia Básica e Clínica, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, RJ 21941-590, Brazil.
Touza
Natália A
NA
Pimenta
Paulo H C
PH
Leitão
Fernanda B
FB
Neto
Chaquip D
CD
da Silva
Alcides J M
AJ
Costa
Paulo R R
PR
Noël
François
F
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D017301:Ca(2+) Mg(2+)-ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism; D020134:Catalytic Domain; D003374:Coumarins / Q000494:pharmacology*; D004229:Dithiothreitol / Q000737:chemistry / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D010084:Oxidation-Reduction; D054328:Proton Pump Inhibitors; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism
C495408:2-methoxy-3,8,9-trihydroxy coumestan; D000925:Anticoagulants; D003374:Coumarins; D004791:Enzyme Inhibitors; D007529:Isoflavones; D054328:Proton Pump Inhibitors; D013438:Sulfhydryl Compounds; D017301:Ca(2+) Mg(2+)-ATPase; D017506:H(+)-K(+)-Exchanging ATPase; D000254:Sodium-Potassium-Exchanging ATPase; C505898:coumestan; D004229:Dithiothreitol