A Novel Atypical PKC-Iota Inhibitor, Echinochrome A, Enhances Cardiomyocyte Differentiation from Mouse Embryonic Stem Cells
AbstractEchinochrome A (EchA) is a marine bioproduct extracted from sea urchins having antioxidant, antimicrobial, anti-inflammatory, and chelating effects, and is the active component of the clinical drug histochrome. We investigated the potential use of Ech A for inducing cardiomyocyte differentiation from mouse embryonic stem cells (mESCs). We also assessed the effects of Ech A on mitochondrial mass, inner membrane potential (Δψm), reactive oxygen species generation, and levels of Ca2+. To identify the direct target of Ech A, we performed in vitro kinase activity and surface plasmon resonance binding assays. Ech A dose-dependently enhanced cardiomyocyte differentiation with higher beating rates. Ech A (50 μM) increased the mitochondrial mass and membrane potential but did not alter the mitochondrial superoxide and Ca2+ levels. The in vitro kinase activity of the atypical protein kinase C-iota (PKCι) was significantly decreased by 50 μM of Ech A with an IC50 for PKCι activity of 107 μM. Computational protein-ligand docking simulation results suggested the direct binding of Ech A to PKCι, and surface plasmon resonance confirmed the direct binding with a low KD of 6.3 nM. Therefore, Ech A is a potential drug for enhancing cardiomyocyte differentiation from mESCs through direct binding to PKCι and inhibition of its activity. View Full-Text
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Kim, H.K.; Cho, S.W.; Heo, H.J.; Jeong, S.H.; Kim, M.; Ko, K.S.; Rhee, B.D.; Mishchenko, N.P.; Vasileva, E.A.; Fedoreyev, S.A.; Stonik, V.A.; Han, J. A Novel Atypical PKC-Iota Inhibitor, Echinochrome A, Enhances Cardiomyocyte Differentiation from Mouse Embryonic Stem Cells. Mar. Drugs 2018, 16, 192.
Kim HK, Cho SW, Heo HJ, Jeong SH, Kim M, Ko KS, Rhee BD, Mishchenko NP, Vasileva EA, Fedoreyev SA, Stonik VA, Han J. A Novel Atypical PKC-Iota Inhibitor, Echinochrome A, Enhances Cardiomyocyte Differentiation from Mouse Embryonic Stem Cells. Marine Drugs. 2018; 16(6):192.Chicago/Turabian Style
Kim, Hyoung K.; Cho, Sung W.; Heo, Hye J.; Jeong, Seung H.; Kim, Min; Ko, Kyung S.; Rhee, Byoung D.; Mishchenko, Natalia P.; Vasileva, Elena A.; Fedoreyev, Sergey A.; Stonik, Valentin A.; Han, Jin. 2018. "A Novel Atypical PKC-Iota Inhibitor, Echinochrome A, Enhances Cardiomyocyte Differentiation from Mouse Embryonic Stem Cells." Mar. Drugs 16, no. 6: 192.
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