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

• DOI: 10.3390/md16060192
• Publication Date: 2018-06-04T12:40:39Z
• Authors: Hyoung Kim; Sung Cho; Hye Heo; Seung Jeong; Min Kim; Kyung Ko; Byoung Rhee; Natalia Mishchenko; Elena Vasileva; Sergey Fedoreyev; Valentin Stonik; Jin Han
• Keywords: Membrane Potential, Mitochondrial; echinochrome A; 0303 health sciences; PKC-iota; QH301-705.5; Communication; Cell Differentiation; Mouse Embryonic Stem Cells; embryonic stem cell; cardiomyocyte differentiation; Mitochondria; Isoenzymes; Mice; 03 medical and health sciences; Animals; Calcium; Myocytes, Cardiac; 14. Life underwater; Biology (General); Reactive Oxygen Species; Cells, Cultured; Protein Kinase C; Naphthoquinones

Echinochrome A (EchA) is a marine bioproduct extracted from sea urchins having antioxidant, antimicrobial, anti-inflammatory, and chelating effects, the active component of clinical drug histochrome. We investigated potential use Ech for inducing cardiomyocyte differentiation mouse embryonic stem cells (mESCs). also assessed effects on mitochondrial mass, inner membrane (Δψm), reactive oxygen species generation, levels Ca2+. To identify direct target A, we performed in vitro kinase activity surface plasmon resonance binding assays. dose-dependently enhanced with higher beating rates. (50 μM) increased mass but did not alter superoxide Ca2+ levels. The atypical protein C-iota (PKCι) was significantly decreased by 50 μM an IC50 PKCι 107 μM. Computational protein-ligand docking simulation results suggested to PKCι, confirmed low KD 6.3 nM. Therefore, enhancing mESCs through inhibition its activity.