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Echinochrome A regulates phosphorylation of phospholamban Ser16 and Thr17 suppressing cardiac SERCA2A Ca2+ reuptake
Kim, H.; Youm, J.; Jeong, S.; Lee, S.; Song, I.; Ko, T.; Pronto, J.; Ko, K.; Rhee, B.; Kim, N.; Nilius, B.; Mischchenko, N.; Fedoreyev, S.; Stonik, V.; Han, J. (2015). Echinochrome A regulates phosphorylation of phospholamban Ser16 and Thr17 suppressing cardiac SERCA2A Ca2+ reuptake. Pflügers Arch. Eur. J. Physiol. 467(10): 2151-2163. https://dx.doi.org/10.1007/s00424-014-1648-2
In: Pflügers Archiv - European Journal of Physiology. Springer: Berlin. ISSN 0031-6768; e-ISSN 1432-2013
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| Trefwoord |
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| Author keywords |
Echinochrome A; Negative inotropic effect; SERCA2A inhibition;Phospholamban phosphorylation |
| Auteurs | | Top |
- Kim, H.
- Youm, J.
- Jeong, S.
- Lee, S.
- Song, I.
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- Ko, T.
- Pronto, J.
- Ko, K.
- Rhee, B.
- Kim, N.
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- Nilius, B.
- Mischchenko, N.
- Fedoreyev, S.
- Stonik, V.
- Han, J.
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| Abstract |
Echinochrome A (Ech A), a marine bio-product isolated from sea urchin eggs, is known to have cardioprotective effects through its strong antioxidant and ATP-sparing capabilities. However, the effects of Ech A on cardiac excitation–contraction (E-C) are not known. In this study, we investigated the effects of Ech A on cardiac contractility and Ca2+ handling in the rat heart. In ex vivo Langendorff hearts, Ech A (3 µM) decreased left ventricular developing pressure to 77.7?±?6.5 % of basal level. In isolated ventricular myocytes, Ech A reduced the fractional cell shortening from 3.4 % at baseline to 2.1 %. Ech A increased both diastolic and peak systolic intracellular Ca2+ ([Ca2+]i). However, the ratio of peak [Ca]i to resting [Ca]i was significantly decreased. Ech A did not affect the L-type Ca2+ current. Inhibiting the Na+/Ca2+ exchanger with either NiCl2 or SEA400 did not affect the Ech A-dependent changes in Ca2+ handling. Our data demonstrate that treatment with Ech A results in a significant reduction in the phosphorylation of phospholamban at both serine 16 and threonine 17 leading to a significant inhibition of SR Ca2+-ATPase 2A (SERCA2A) and subsequent reduced Ca2+ uptake into the intracellular Ca2+ store. Taken together, our data show that Ech A negatively regulates cardiac contractility by inhibiting SERCA2A activity, which leads to a reduction in internal Ca2+ stores. |
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