2. Academic Validation
  3. Echinochrome A regulates phosphorylation of phospholamban Ser16 and Thr17 suppressing cardiac SERCA2A Ca²⁺ reuptake

Echinochrome A regulates phosphorylation of phospholamban Ser16 and Thr17 suppressing cardiac SERCA2A Ca²⁺ reuptake

  • Pflugers Arch. 2015 Oct;467(10):2151-63. doi: 10.1007/s00424-014-1648-2.
Hyoung Kyu Kim 1 2,  Jae Boum Youm 1 2,  Seung Hun Jeong 1 2,  Sung Ryul Lee 1 2,  In-Sung Song 1 2,  Tae Hee Ko 1 2,  Julius Ryan Pronto 1 2,  Kyung Soo Ko 1 2,  Byoung Doo Rhee 1 2,  Nari Kim 1 2,  Bernd Nilius 3,  Natalia P Mischchenko 4,  Sergey A Fedoreyev 4,  Valentin A Stonik 4,  Jin Han 5 6
Affiliations

Affiliations

  • 1 Cardiovascular and Metabolic Disease Center (CMDC), National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Inje University, Busan, South Korea.
  • 2 Department of Health Sciences and Technology, Graduate School of Inje University, Busan, South Korea.
  • 3 Department Cell Molecular Medicine, Laboratory Ion Channel Research, Campus Gasthuisberg, KU Leuven, Leuven, Belgium.
  • 4 G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Prospect 100 let Vladivostoku, 159, Vladivostok, 690022, Russia.
  • 5 Cardiovascular and Metabolic Disease Center (CMDC), National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Inje University, Busan, South Korea. [email protected].
  • 6 Department of Health Sciences and Technology, Graduate School of Inje University, Busan, South Korea. [email protected].
PMID: 25410495 DOI: 10.1007/s00424-014-1648-2
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 Ca(2+) 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 Ca(2+) ([Ca(2+)]i). However, the ratio of peak [Ca]i to resting [Ca]i was significantly decreased. Ech A did not affect the L-type Ca(2+) current. Inhibiting the Na(+)/Ca(2+) exchanger with either NiCl2 or SEA400 did not affect the Ech A-dependent changes in Ca(2+) 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 Ca(2+)-ATPase 2A (SERCA2A) and subsequent reduced Ca(2+) uptake into the intracellular Ca(2+) store. Taken together, our data show that Ech A negatively regulates cardiac contractility by inhibiting SERCA2A activity, which leads to a reduction in internal Ca(2+) stores.

Keywords

Echinochrome A; Negative inotropic effect; Phospholamban phosphorylation; SERCA2A inhibition.

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