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Title: Echinochrome A regulates phosphorylation of phospholamban Ser16 and Thr17 suppressing cardiac SERCA2A Ca(2+) reuptake
Authors: Kim, Hyoung Kyu ×
Youm, Jae Boum
Jeong, Seung Hun
Lee, Sung Ryul
Song, In-Sung
Ko, Tae Hee
Pronto, Julius Ryan
Ko, Kyung Soo
Rhee, Byoung Doo
Kim, Nari
Nilius, Bernd
Mischchenko, Natalia P
Fedoreyev, Sergey A
Stonik, Valentin A
Han, Jin #
Issue Date: Oct-2015
Publisher: Springer-Verlag
Series Title: Pflügers Archiv: European Journal of Physiology vol:467 issue:10 pages:2151-2163
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.
URI: 
ISSN: 0031-6768
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Cellular and Molecular Medicine - miscellaneous
× corresponding author
# (joint) last author

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