12-O-Tetradecanoylphor bol-13-acetate increases cardiomyogenesis through PKC/ERK signaling

0537569 - BFÚ 2021 RIV GB eng J - Journal Article
Radaszkiewicz, K. A. - Beckerov, D. - Woloszczukov, L. - Radaszkiewicz, T.W. - Lesakov, P. - Blanářová, O. - Kubala, Lukáš - Humpolíček, P. - Pacherník, J.
12-O-Tetradecanoylphor bol-13-acetate increases cardiomyogenesis through PKC/ERK signaling.
Scientific Reports. Roč. 10, č. 1 (2020), č. článku 15922. ISSN 2045-2322. E-ISSN 2045-2322
Institutional support: RVO:68081707
Keywords : protein-kinase-c * embryonic stem-cells * transcription factor gata4 * hl-60 cells * differentiation * cardiomyocytes
OECD category: Biophysics
Impact factor: 4.380, year: 2020
Method of publishing: Open access
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12-O-Tetradecanoylphorbol-13-acetate (TPA) is the most widely used diacylglycerol (DAG) mimetic agent and inducer of protein kinase C (PKC)-mediated cellular response in biomedical studies. TPA has been proposed as a pluripotent cell differentiation factor, but results obtained have been inconsistent. In the present study we show that TPA can be applied as a cardiomyogenesis-promoting factor for the differentiation of mouse embryonic stem (mES) cells in vitro. The mechanism of TPA action is mediated by the induction of extracellular signal-regulated kinase (ERK) activity and the subsequent phosphorylation of GATA4 transcription factor. Interestingly, general mitogens (FGF, EGF, VEGF and serum) or canonical WNT signalling did not mimic the effect of TPA. Moreover, on the basis of our results, we postulate that a TPA-sensitive population of cardiac progenitor cells exists at a certain time point (after days 6-8 of the differentiation protocol) and that the proposed treatment can be used to increase the multiplication of ES cell-derived cardiomyocytes.
Permanent Link: http://hdl.handle.net/11104/0315400