0471949 - BFÚ 2017 RIV DK eng J - Journal Article
Kudová, Jana - Vašíček, Ondřej - Číž, Milan - Kubala, Lukáš
Melatonin promotes cardiomyogenesis of embryonic stem cells via inhibition of HIF-1 alpha stabilization.
Journal of Pineal Research. Roč. 61, č. 4 (2016), s. 493-503. ISSN 0742-3098. E-ISSN 1600-079X
R&D Projects: GA MŠMT(CZ) LD14030
Institutional support: RVO:68081707
Keywords : prostate-cancer cells * increased vascular-permeability * reperfusion injury
Subject RIV: BO - Biophysics
Impact factor: 10.391, year: 2016 ; AIS: 1.23, rok: 2016
DOI: https://doi.org/10.1111/jpi.12366

Melatonin, a molecule involved in the regulation of circadian rhythms, has protective effects against myocardial injuries. However, its capability to regulate the maturation of cardiac progenitor cells is unclear. Recently, several studies have shown that melatonin inhibits the stabilization of hypoxia-inducible factors (HIFs), important signaling molecules with cardioprotective effects. In this study, by employing differentiating mouse embryonic stem cells, we report that melatonin significantly upregulated the expression of cardiac cell-specific markers (myosin heavy chains six and seven) as well as the percentage of myosin heavy chain-positive cells. Importantly, melatonin decreased HIF-1 alpha stabilization and transcriptional activity and, in contrast, induced HIF-2 alpha stabilization. Interestingly, the deletion of HIF-1 alpha completely inhibited the pro-cardiomyogenic effect of melatonin as well as the melatonin-mediated HIF-2 alpha stabilization. Moreover, melatonin increased Sirt-1 levels in a HIF-1 alpha-dependent manner. Taken together, we provide new evidence of a time-specific inhibition of HIF-1 alpha stabilization as an essential feature of melatonin-induced cardiomyogenesis and unexpected different roles of HIF-1 alpha stabilization during various stages of cardiac development. These results uncover new mechanisms underlying the maturation of cardiac progenitor cells and can help in the development of novel strategies for using melatonin in cardiac regeneration therapy.
Permanent Link: http://hdl.handle.net/11104/0269311