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• W2045120149 endingPage "531" @default.
• W2045120149 startingPage "523" @default.
• W2045120149 abstract "The interactions of tamoxifen (TAM) and its active metabolite 4-hydroxytamoxifen (OHTAM) with the sarcoplasmic reticulum (SR) Ca2+-pump were investigated. The turnover of the Ca2+-ATPase is strongly inhibited by both drugs at low concentrations that do not significantly perturb the lipid organization of SR membranes. Moreover, TAM decreases Ca2+ accumulation by SR Ca2+-ATPase and increases in parallel the ATP hydrolysis, decreasing the energetic efficiency of the Ca2+-pump (Ca2+ATP coupling ratio) by about 70% at 30 μM. This uncoupling of ATP hydrolysis from Ca2+ accumulation is a putative consequence of structural defects induced on membranes, since the ATP hydrolysis at low residual Ca2+ (Ca2+ not supplemented) is also stimulated. On the other hand, OHTAM decreases the Ca2+ uptake to a greater extent than TAM but, unlike TAM, it inhibits ATP hydrolysis. Thus, the Ca2+ATP ratio is decreased by about 47% at 30 μM OHTAM; this effect is not a consequence of membrane disruption, since the ATP-splitting activity decreases in parallel to Ca2+ accumulation and no significant effect is detected for ATP hydrolysis at low residual Ca2+. The inhibition of the Ca2+-pump by OHTAM is putatively related to a direct interaction with the regulatory sites of the enzyme or interactive perturbations at the lipid-protein interface. The effect may result from a decrease of efficiency in the energy transmission and transduction between the ATP use at the catalytic site and the channeling process involved in Ca2+ translocation. Therefore, the effects of the drugs on the Ca2+-pump are different and rule out an unitary mechanism of action on the basis of bilayer structure perturbations." @default.
• W2045120149 created "2016-06-24" @default.
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• W2045120149 date "1996-10-01" @default.
• W2045120149 modified "2023-10-18" @default.
• W2045120149 title "The effect of the anticancer drugs tamoxifen and hydroxytamoxifen on the calcium pump of isolated sarcoplasmic reticulum vesicles" @default.
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• W2045120149 doi "https://doi.org/10.1016/s0887-2333(96)00040-9" @default.
• W2045120149 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20650233" @default.
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