Abstract
Green tea polyphenolic catechins exhibit biological activity in a wide variety of cell types. Although reports in the lay and scientific literature suggest therapeutic potential for improving cardiovascular health, the underlying molecular mechanisms of action remain unclear. Previous studies have implicated a wide range of molecular targets in cardiac muscle for the major green tea catechin, (-)-epigallocatechin-3-gallate (EGCG), but effects were observed only at micromolar concentrations of unclear clinical relevance. Here, we report that nanomolar concentrations of EGCG significantly enhance contractility of intact murine myocytes by increasing electrically evoked Ca2+ transients, sarcoplasmic reticulum (SR) Ca2+ content, and ryanodine receptor type 2 (RyR2) channel open probability. Voltageclamp experiments demonstrate that 10 nM EGCG significantly inhibits the Na +-Ca2+ exchanger. Of importance, other Na+ and Ca2+ handling proteins such as Ca2+-ATPase, Na +-H+ exchanger, and Na+-K+-ATPase were not affected by EGCG ≤1 μM. Thus, nanomolar EGCG increases contractility in intact myocytes by coordinately modulating SR Ca2+ loading, RyR2- mediated Ca2+ release, and Na+-Ca 2+ exchange. Inhibition of Na+-K+-ATPase activity probably contributes to the positive inotropic effects observed at EGCG concentrations >1 μM. These newly recognized actions of nanomolar and micromolar EGCG should be considered when the therapeutic and toxicological potential of green tea supplementation is evaluated and may provide a novel therapeutic strategy for improving contractile function in heart failure.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 993-1000 |
| Number of pages | 8 |
| Journal | Molecular Pharmacology |
| Volume | 82 |
| Issue number | 5 |
| DOIs | |
| State | Published - Nov 2012 |
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ASJC Scopus subject areas
- Pharmacology
- Molecular Medicine
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Coordinated regulation of murine cardiomyocyte contractility by nanomolar (-)-epigallocatechin-3-gallate, the major green tea catechin. / Feng, Wei; Hwang, Hyun Seok; Kryshtal, Dmytro O.; Yang, Tao; Padilla, Isela T.; Tiwary, Asheesh K.; Puschner, Birgit; Pessah, Isaac N; Knollmann, Björn C.
In: Molecular Pharmacology, Vol. 82, No. 5, 11.2012, p. 993-1000.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Coordinated regulation of murine cardiomyocyte contractility by nanomolar (-)-epigallocatechin-3-gallate, the major green tea catechin
AU - Feng, Wei
AU - Hwang, Hyun Seok
AU - Kryshtal, Dmytro O.
AU - Yang, Tao
AU - Padilla, Isela T.
AU - Tiwary, Asheesh K.
AU - Puschner, Birgit
AU - Pessah, Isaac N
AU - Knollmann, Björn C.
PY - 2012/11
Y1 - 2012/11
N2 - Green tea polyphenolic catechins exhibit biological activity in a wide variety of cell types. Although reports in the lay and scientific literature suggest therapeutic potential for improving cardiovascular health, the underlying molecular mechanisms of action remain unclear. Previous studies have implicated a wide range of molecular targets in cardiac muscle for the major green tea catechin, (-)-epigallocatechin-3-gallate (EGCG), but effects were observed only at micromolar concentrations of unclear clinical relevance. Here, we report that nanomolar concentrations of EGCG significantly enhance contractility of intact murine myocytes by increasing electrically evoked Ca2+ transients, sarcoplasmic reticulum (SR) Ca2+ content, and ryanodine receptor type 2 (RyR2) channel open probability. Voltageclamp experiments demonstrate that 10 nM EGCG significantly inhibits the Na +-Ca2+ exchanger. Of importance, other Na+ and Ca2+ handling proteins such as Ca2+-ATPase, Na +-H+ exchanger, and Na+-K+-ATPase were not affected by EGCG ≤1 μM. Thus, nanomolar EGCG increases contractility in intact myocytes by coordinately modulating SR Ca2+ loading, RyR2- mediated Ca2+ release, and Na+-Ca 2+ exchange. Inhibition of Na+-K+-ATPase activity probably contributes to the positive inotropic effects observed at EGCG concentrations >1 μM. These newly recognized actions of nanomolar and micromolar EGCG should be considered when the therapeutic and toxicological potential of green tea supplementation is evaluated and may provide a novel therapeutic strategy for improving contractile function in heart failure.
AB - Green tea polyphenolic catechins exhibit biological activity in a wide variety of cell types. Although reports in the lay and scientific literature suggest therapeutic potential for improving cardiovascular health, the underlying molecular mechanisms of action remain unclear. Previous studies have implicated a wide range of molecular targets in cardiac muscle for the major green tea catechin, (-)-epigallocatechin-3-gallate (EGCG), but effects were observed only at micromolar concentrations of unclear clinical relevance. Here, we report that nanomolar concentrations of EGCG significantly enhance contractility of intact murine myocytes by increasing electrically evoked Ca2+ transients, sarcoplasmic reticulum (SR) Ca2+ content, and ryanodine receptor type 2 (RyR2) channel open probability. Voltageclamp experiments demonstrate that 10 nM EGCG significantly inhibits the Na +-Ca2+ exchanger. Of importance, other Na+ and Ca2+ handling proteins such as Ca2+-ATPase, Na +-H+ exchanger, and Na+-K+-ATPase were not affected by EGCG ≤1 μM. Thus, nanomolar EGCG increases contractility in intact myocytes by coordinately modulating SR Ca2+ loading, RyR2- mediated Ca2+ release, and Na+-Ca 2+ exchange. Inhibition of Na+-K+-ATPase activity probably contributes to the positive inotropic effects observed at EGCG concentrations >1 μM. These newly recognized actions of nanomolar and micromolar EGCG should be considered when the therapeutic and toxicological potential of green tea supplementation is evaluated and may provide a novel therapeutic strategy for improving contractile function in heart failure.
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U2 - 10.1124/mol.112.079707
DO - 10.1124/mol.112.079707
M3 - Article
VL - 82
SP - 993
EP - 1000
JO - Molecular Pharmacology
JF - Molecular Pharmacology
SN - 0026-895X
IS - 5
ER -