Demethoxycurcumin is a potent inhibitor of P-type ATPases from diverse kingdoms of life

Trong Tuan Dao, Pankaj Sehgal, Truong Thanh Tung, Jesper Vuust Møller, John Nielsen, Michael Broberg Palmgren, Søren Brøgger Christensen, Anja Thoe Fuglsang

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Abstract

P-type ATPases catalyze the active transport of cations and phospholipids across biological membranes. Members of this large family are involved in a range of fundamental cellular processes. To date, a substantial number of P-type ATPase inhibitors have been characterized, some of which are used as drugs. In this work a library of natural compounds was screened and we first identified curcuminoids as plasma membrane H+-ATPases inhibitors in plant and fungal cells. We also found that some of the commercial curcumins contain several curcuminoids. Three of these were purified and, among the curcuminoids, demethoxycurcumin was the most potent inhibitor of all tested P-type ATPases from fungal (Pma1p; H+-ATPase), plant (AHA2; H+-ATPase) and animal (SERCA; Ca2+-ATPase) cells. All three curcuminoids acted as non-competitive antagonist to ATP and hence may bind to a highly conserved allosteric site of these pumps. Future research on biological effects of commercial preparations of curcumin should consider the heterogeneity of the material.

OriginalsprogEngelsk
Artikelnummere0163260
TidsskriftP L o S One
Vol/bind11
Udgave nummer9
Antal sider19
ISSN1932-6203
DOI
StatusUdgivet - 2016

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