title: Echinochrome A regulates phosphorylation of phospholamban Ser16 and Thr17 suppressing cardiac SERCA2A Ca²⁺ reuptake.
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.
authors.affiliation: Cardiovascular and Metabolic Disease Center (CMDC), National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Inje University, Busan, South Korea.|Department of Health Sciences and Technology, Graduate School of Inje University, Busan, South Korea.
authors.forename: Hyoung Kyu
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Cardiovascular and Metabolic Disease Center (CMDC), National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Inje University, Busan, South Korea.|Department of Health Sciences and Technology, Graduate School of Inje University, Busan, South Korea.
authors.forename: Jae Boum
authors.initials: JB
authors.lastname: Youm
authors.affiliation: Cardiovascular and Metabolic Disease Center (CMDC), National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Inje University, Busan, South Korea.|Department of Health Sciences and Technology, Graduate School of Inje University, Busan, South Korea.
authors.forename: Seung Hun
authors.initials: SH
authors.lastname: Jeong
authors.affiliation: Cardiovascular and Metabolic Disease Center (CMDC), National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Inje University, Busan, South Korea.|Department of Health Sciences and Technology, Graduate School of Inje University, Busan, South Korea.
authors.forename: Sung Ryul
authors.initials: SR
authors.lastname: Lee
authors.affiliation: Cardiovascular and Metabolic Disease Center (CMDC), National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Inje University, Busan, South Korea.|Department of Health Sciences and Technology, Graduate School of Inje University, Busan, South Korea.
authors.forename: In-Sung
authors.initials: IS
authors.lastname: Song
authors.affiliation: Cardiovascular and Metabolic Disease Center (CMDC), National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Inje University, Busan, South Korea.|Department of Health Sciences and Technology, Graduate School of Inje University, Busan, South Korea.
authors.forename: Tae Hee
authors.initials: TH
authors.lastname: Ko
authors.affiliation: Cardiovascular and Metabolic Disease Center (CMDC), National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Inje University, Busan, South Korea.|Department of Health Sciences and Technology, Graduate School of Inje University, Busan, South Korea.
authors.forename: Julius Ryan
authors.initials: JR
authors.lastname: Pronto
authors.affiliation: Cardiovascular and Metabolic Disease Center (CMDC), National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Inje University, Busan, South Korea.|Department of Health Sciences and Technology, Graduate School of Inje University, Busan, South Korea.
authors.forename: Kyung Soo
authors.initials: KS
authors.lastname: Ko
authors.affiliation: Cardiovascular and Metabolic Disease Center (CMDC), National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Inje University, Busan, South Korea.|Department of Health Sciences and Technology, Graduate School of Inje University, Busan, South Korea.
authors.forename: Byoung Doo
authors.initials: BD
authors.lastname: Rhee
authors.affiliation: Cardiovascular and Metabolic Disease Center (CMDC), National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Inje University, Busan, South Korea.|Department of Health Sciences and Technology, Graduate School of Inje University, Busan, South Korea.
authors.forename: Nari
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department Cell Molecular Medicine, Laboratory Ion Channel Research, Campus Gasthuisberg, KU Leuven, Leuven, Belgium.
authors.forename: Bernd
authors.initials: B
authors.lastname: Nilius
authors.affiliation: 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.
authors.forename: Natalia P
authors.initials: NP
authors.lastname: Mischchenko
authors.affiliation: 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.
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Fedoreyev
authors.affiliation: 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.
authors.forename: Valentin A
authors.initials: VA
authors.lastname: Stonik
authors.affiliation: Cardiovascular and Metabolic Disease Center (CMDC), National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Inje University, Busan, South Korea. phyhanj@gmail.com.|Department of Health Sciences and Technology, Graduate School of Inje University, Busan, South Korea. phyhanj@gmail.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Han
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009285:Naphthoquinones / Q000494:pharmacology*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D016276:Ventricular Function; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D002316:Cardiotonic Agents; D009285:Naphthoquinones; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D012694:Serine; D013912:Threonine; D000099211:Phospholamban; C007573:echinochrome A
keywords: Echinochrome A; Negative inotropic effect; Phospholamban phosphorylation; SERCA2A inhibition