1 Institute of Biophysics, Faculty of Health Sciences, Aarhus University, Aarhus University2 Department of Biomedicine - Forskning og uddannelse, Vest, Department of Biomedicine, Health, Aarhus University3 Department of Biomedicine - Forskning og uddannelse, Vest, Department of Biomedicine, Health, Aarhus University
Curcumin, the major constitute of tumeric, is an important nutraceutical that has been shown to be useful in the treatment of many diseases. As an inhibitor of the sarcoplasmic reticulum Ca2+-ATPase, curcumin was shown to correct cystic fibrosis (CF) defects in some model systems, whereas others have reported no or little effects on CF after curcumin treatment, suggesting that curcumin effect is not due to simple inhibition of the Ca2+-ATPase. We tested the hypothesis that curcumin may modulate other members of the P2-type ATPase superfamily by studying the effects of curcumin on the activity and kinetic properties of the Na,K-ATPase. Curcumin treatment inhibited Na,K-ATPase activity in a dose-dependent manner (K0.514.6 M). Curcumin decreased the apparent affinity of Na,K-ATPase for K+ and increased it for Na+ and ATP. Kinetic analyses indicated that curcumin induces a three-fold reduction in the rate of E1P E2P transition, thereby increasing the steady-state phosphoenzyme level. Curcumin treatment significantly abrogated K+ occlusion to the enzyme as evidenced from kinetic and proteolytic cleavage experiments. Curcumin also significantly decreased the vanadate sensitivity of the enzyme. Thus, curcumin partially blocks the K+ occlusion site, and induces a constitutive shift in the conformational equilibrium of the enzyme, towards the E1 conformation. The physiological consequences of curcumin treatment previously reported in different epithelial model systems may, at least in part, be related to the direct effects of curcumin on Na,K-ATPase activity.
British Journal of Pharmacology, 2005, Vol 125, Issue 2, p. 236-245