Inhibition of SERCA and PMCA Ca2+-ATPase activities by polyoxotungstates

Abstract

Plasma membrane calcium ATPases (PMCA) and sarco(endo) reticulum calcium ATPases (SERCA) are key proteins in the maintenance of calcium homeostasis. Herein, we compare for the first time the inhibition of SERCA and PMCA calcium pumps by several polyoxotungstates (POTs), namely by Wells-Dawson phosphotungstate anions [P₂W₁₈O₆₂]^6- (intact, {P₂W₁₈}), [P₂W₁₇O₆₁]^10- (monolacunary, {P₂W₁₇}), [P₂W₁₅O₅₆]^12- (trilacunary, {P₂W₁₅}), [H₂P₂W₁₂O₄₈]^12- (hexalacunary, {P₂W₁₂}), [H₃P₂W₁₅V₃O₆₂]^6- (trivanadium-substituted, {P₂W₁₅V₃}) and by Preyssler-type anion [NaP₅W₃₀O₁₁₀]^14- ({P₅W₃₀}). The speciation in the solutions of tested POTs was investigated by ³¹P and ⁵¹V NMR spectroscopy. The tested POTs inhibited SERCA Ca²⁺-ATPase activity, whereby the Preyssler POT showed the strongest effect, with an IC₅₀ value of 0.37 μM. For {P₂W₁₇} and {P₂W₁₅V₃} higher IC₅₀ values were determined: 0.72 and 0.95 μM, respectively. The studied POTs showed to be more potent inhibitors of PMCA Ca²⁺-ATPase activity, with lower IC₅₀ values for {P₂W₁₇}, {P₅W₃₀} and {P₂W₁₅V₃}.

Keywords: ATPases inhibitors; Anticancer drugs; Ca(2+)-ATPase; Drug discovery; Polyoxometalate's stability; Polyoxometalates.