Next Article in Journal
Commercial Fucoidans from Fucus vesiculosus Can Be Grouped into Antiadipogenic and Adipogenic Agents
Next Article in Special Issue
(−)-Homosalinosporamide A and Its Mode of Proteasome Inhibition: An X-ray Crystallographic Study
Previous Article in Journal
Heterologous Expression of a VioA Variant Activates Cryptic Compounds in a Marine-Derived Brevibacterium Strain
Previous Article in Special Issue
Molecular Targets of Active Anticancer Compounds Derived from Marine Sources
Article Menu
Issue 6 (June) cover image

Export Article

Open AccessCommunication
Mar. Drugs 2018, 16(6), 192; https://doi.org/10.3390/md16060192

A Novel Atypical PKC-Iota Inhibitor, Echinochrome A, Enhances Cardiomyocyte Differentiation from Mouse Embryonic Stem Cells

1
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, Department of Health Sciences and Technology, BK21 Plus Project Team, Cardiovascular and Metabolic Disease Center, Inje University College of Medicine, Busan 47392, Korea
2
Department of Integrated Biomedical Science, Inje University College of Medicine, Busan 47392, Korea
3
Division of Cardiology, Department of Internal Medicine, Inje University College of Medicine, Seoul Paik Hospital, Seoul 04551, Korea
4
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Vladivostok 690022, Russia
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 16 May 2018 / Revised: 31 May 2018 / Accepted: 1 June 2018 / Published: 2 June 2018
(This article belongs to the Special Issue Marine Drugs Interact with Functional Proteins)
View Full-Text   |   Download PDF [3454 KB, uploaded 5 June 2018]   |  

Abstract

Echinochrome 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
Keywords: echinochrome A; embryonic stem cell; cardiomyocyte differentiation; PKC-iota echinochrome A; embryonic stem cell; cardiomyocyte differentiation; PKC-iota
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Mar. Drugs EISSN 1660-3397 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top