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

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• 作者：Hyoung Kyu Kim ; Jae Boum Youm…
• 关键词：Echinochrome A ; Negative inotropic effect ; SERCA2A inhibition ; Phospholamban phosphorylation
• 刊名：Pfl篓鹿gers Archiv - European Journal of Physiology
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：467
• 期：10
• 页码：2151-2163
• 全文大小：1,733 KB
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• 作者单位：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 (1) (2)
  
  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
  
• 刊物主题：Human Physiology;
• 出版者：Springer Berlin Heidelberg
• ISSN：1432-2013

文摘

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?±-.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. Keywords Echinochrome A Negative inotropic effect SERCA2A inhibition Phospholamban phosphorylation