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Curcumin, a molecule that inhibits the Ca2+-ATPase of sarcoplasmic reticulum but increases the rate of accumulation of Ca2+

Curcumin, a molecule that inhibits the Ca2+-ATPase of sarcoplasmic reticulum but increases the rate of accumulation of Ca2+
Curcumin, a molecule that inhibits the Ca2+-ATPase of sarcoplasmic reticulum but increases the rate of accumulation of Ca2+
Curcumin, an important inhibitor of carcinogenesis, is an inhibitor of the ATPase activity of the Ca2+-ATPase of skeletal muscle sarcoplasmic reticulum (SR). Inhibition by curcumin is structurally specific, requiring the presence of a pair of -OH groups at the 4-position of the rings. Inhibition is not competitive with ATP. Unexpectedly, addition of curcumin to SR vesicles leads to an increase in the rate of accumulation of Ca2+, unlike other inhibitors of the Ca2+-ATPase that result in a reduced rate of accumulation. An increase in the rate of accumulation of Ca2+ 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 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. The structural specificity of the effects of curcumin on ATPase activity and on Ca2+ accumulation is the same, and the apparent dissociation constants for the two effects are similar, suggesting that the two effects of curcumin could follow from binding to a single site on the ATPase.
0021-9258
46905-46911
Logan-Smith, M.J.
15791841-29af-4d01-abfd-a2b7ac413583
Lockyer, P.J.
6abf6cb6-ebeb-48b6-b0a8-75f0f252f073
East, J.M.
9fe7f794-1d89-4935-9a99-b831d786056e
Lee, A.G.
0891914c-e0e2-4ee1-b43e-1b70eb072d8e
Logan-Smith, M.J.
15791841-29af-4d01-abfd-a2b7ac413583
Lockyer, P.J.
6abf6cb6-ebeb-48b6-b0a8-75f0f252f073
East, J.M.
9fe7f794-1d89-4935-9a99-b831d786056e
Lee, A.G.
0891914c-e0e2-4ee1-b43e-1b70eb072d8e

Logan-Smith, M.J., Lockyer, P.J., East, J.M. and Lee, A.G. (2001) Curcumin, a molecule that inhibits the Ca2+-ATPase of sarcoplasmic reticulum but increases the rate of accumulation of Ca2+. The Journal of Biological Chemistry, 276 (50), 46905-46911. (doi:10.1074/jbc.M108778200).

Record type: Article

Abstract

Curcumin, an important inhibitor of carcinogenesis, is an inhibitor of the ATPase activity of the Ca2+-ATPase of skeletal muscle sarcoplasmic reticulum (SR). Inhibition by curcumin is structurally specific, requiring the presence of a pair of -OH groups at the 4-position of the rings. Inhibition is not competitive with ATP. Unexpectedly, addition of curcumin to SR vesicles leads to an increase in the rate of accumulation of Ca2+, unlike other inhibitors of the Ca2+-ATPase that result in a reduced rate of accumulation. An increase in the rate of accumulation of Ca2+ 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 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. The structural specificity of the effects of curcumin on ATPase activity and on Ca2+ accumulation is the same, and the apparent dissociation constants for the two effects are similar, suggesting that the two effects of curcumin could follow from binding to a single site on the ATPase.

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Published date: 1 December 2001

Identifiers

Local EPrints ID: 55987
URI: http://eprints.soton.ac.uk/id/eprint/55987
ISSN: 0021-9258
PURE UUID: 3fead6bf-c911-4d6c-ba98-8eea2c129f59

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Date deposited: 07 Aug 2008
Last modified: 15 Mar 2024 10:59

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Contributors

Author: M.J. Logan-Smith
Author: P.J. Lockyer
Author: J.M. East
Author: A.G. Lee

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