Effects of Phytoestrogens on Sarcoplasmic/Endoplasmic Reticulum Calcium ATPase 2a and Ca2+ Uptake into Cardiac Sarcoplasmic Reticulum

Phytoestrogens are naturally occurring estrogenic compounds found in plants and plant products. These compounds are also known to exert cellular effects independent of their interactions with estrogen receptors. We studied the effects of the phytoestrogens phloretin, phloridzin, genistein, and bioch...

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Bibliographic Details
Published in:The Journal of pharmacology and experimental therapeutics 2006-02, Vol.316 (2), p.628-635
Main Authors: Olson, Marnie L, Kargacin, Margaret E, Honeyman, Thomas W, Ward, Christopher A, Kargacin, Gary J
Format: Article
Language:English
Subjects:
Animals
Calcium - metabolism
Calcium-Transporting ATPases - metabolism
Dogs
Endoplasmic Reticulum - drug effects
Endoplasmic Reticulum - enzymology
Endoplasmic Reticulum - metabolism
Heart - drug effects
Heart Ventricles - drug effects
Heart Ventricles - enzymology
Heart Ventricles - metabolism
In Vitro Techniques
Intracellular Membranes - drug effects
Intracellular Membranes - enzymology
Intracellular Membranes - metabolism
Myocardium - enzymology
Myocardium - metabolism
Phytoestrogens - pharmacology
Sarcoplasmic Reticulum - drug effects
Sarcoplasmic Reticulum - enzymology
Sarcoplasmic Reticulum - metabolism
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Summary:Phytoestrogens are naturally occurring estrogenic compounds found in plants and plant products. These compounds are also known to exert cellular effects independent of their interactions with estrogen receptors. We studied the effects of the phytoestrogens phloretin, phloridzin, genistein, and biochanin A on Ca 2+ uptake into the cardiac muscle sarcoplasmic reticulum (SR). Genistein and biochanin A did not affect SR Ca 2+ uptake. On the other hand, phloretin and phloridzin decreased the maximum velocity of SR Ca 2+ uptake but did not affect the Hill coefficient or the Ca 2+ sensitivity of uptake. Measurements of the ATPase activity of the cardiac SR Ca 2+ pump (SERCA2a) revealed direct inhibitory effects of phloretin and phloridzin on SERCA2a. Neither compound induced a detectable change in the permeability of the SR membrane to Ca 2+ . These results indicate that phloretin and phloridzin inhibit cardiac SR Ca 2+ uptake by directly inhibiting SERCA2a.
ISSN:0022-3565
1521-0103
DOI:10.1124/jpet.105.092940