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Papers In Press, published online ahead of print October 9, 2001
Department of Biochemistry, University of Southampton, Southampton SO16 7PX
Corresponding Author: agl{at}soton.ac.uk
Curcumin is an important inhibitor of carcinogenesis and an inhibitor of the SERCA class of Ca2+-ATPase. Addition of inhibitors of the Ca2+-ATPase to QT-6 cells leads to an increase in the cytoplasmic concentration of Ca2+ . This increase in Ca2+ concentration is prevented by curcumin. Since xestospongin C, a blocker of IP3-mediated Ca2+ channels has the same effect, it is proposed that curcumin blocks IP3-sensitive Ca2+ channels in endoplasmic reticulum and that IP3-sensitive Ca2+ channels are the normal pathway for leak of Ca2+ from the endoplasmic reticulum. Addition of curcumin to sarcoplasmic reticulum (SR) vesicles leads to an increase in the rate of accumulation of Ca2+, unlike other inhibitors of the Ca2+-ATPase which result in a reduced rate of accumulation. The effect is seen in the presence of phosphate ion, which lowers the concentration of free Ca2+ within the lumen of the SR, showing that the effect is not on passive leak across the SR membrane. Rather, simulations suggest that the effect is to reduce the rate of slippage on the ATPase, a process in which a Ca2+-bound, phosphorylated intermediate releases its bound Ca2+ on the cytoplasmic rather than on the lumenal side of the membrane.
J. Biol. Chem, 10.1074/jbc.M108778200
Submitted on September 12, 2001
Revised on September 27, 2001
Accepted on October 9, 2001
Curcumin, a molecule that inhibits the Ca2+-ATPase of sarcoplasmic reticulum but increases the rate of accumulation of Ca2+
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