Modulation of the low affinity Ca2+-binding sites of skeletal muscle and blood platelets Ca2+-ATPase by nordihydroguaiaretic acid.
The antioxidant nordihydroguaiaretic acid (NDGA) inhibited the different sarco/endoplasmic reticulum Ca2+-ATPase isoforms found in skeletal muscle and blood platelets. For the sarcoplasmic reticulum, but not for the blood platelets Ca2+-ATPase, the concentration of NDGA needed for half-maximal inhibition was found to vary depending on the substrate used and its concentration in the assay medium. The phosphorylation of the sarcoplasmic reticulum Ca2+-ATPase by ATP and by Pi were both inhibited by NDGA. In leaky vesicles, measurements of the ATP<-->Pi exchange showed that NDGA increases the affinity for Ca2+ of the E2 conformation of the enzyme, which has low affinity for Ca2+. The effects of NDGA on the Ca2+-ATPase were not reverted by the reducing agent dithiothreitol nor by the lipid-soluble antioxidant butylated hydroxytoluene.
Instituto de Ciências Biomédicas, Departamento de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Cidade Universitária, Brazil.
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D025181:ATP Synthetase Complexes; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D002118:Calcium / Q000097:blood / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000097:blood / Q000378:metabolism*; D004229:Dithiothreitol / Q000494:pharmacology; D009637:Masoprocol / Q000378:metabolism / Q000494:pharmacology*; D009097:Multienzyme Complexes; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D017856:Phosphotransferases (Phosphate Group Acceptor); D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D000975:Antioxidants; D009097:Multienzyme Complexes; D002084:Butylated Hydroxytoluene; D009637:Masoprocol; D000255:Adenosine Triphosphate; D025181:ATP Synthetase Complexes; D017856:Phosphotransferases (Phosphate Group Acceptor); D000252:Calcium-Transporting ATPases; D002118:Calcium; D004229:Dithiothreitol