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@article{1389151,
author = {Kudová, Jana and Vašíček, Ondřej and Číž, Milan and Kubala, Lukáš},
article_location = {HOBOKEN},
article_number = {4},
doi = {http://dx.doi.org/10.1111/jpi.12366},
keywords = {cardiomyogenesis; hypoxia-inducible factor-alpha; melatonin; mouse embryonic stem cells},
language = {eng},
issn = {0742-3098},
journal = {JOURNAL OF PINEAL RESEARCH},
title = {Melatonin promotes cardiomyogenesis of embryonic stem cells via inhibition of HIF-1 alpha stabilization},
volume = {61},
year = {2016}
}
TY - JOUR
ID - 1389151
AU - Kudová, Jana - Vašíček, Ondřej - Číž, Milan - Kubala, Lukáš
PY - 2016
TI - Melatonin promotes cardiomyogenesis of embryonic stem cells via inhibition of HIF-1 alpha stabilization
JF - JOURNAL OF PINEAL RESEARCH
VL - 61
IS - 4
SP - 493-503
EP - 493-503
PB - WILEY
SN - 07423098
KW - cardiomyogenesis
KW - hypoxia-inducible factor-alpha
KW - melatonin
KW - mouse embryonic stem cells
N2 - 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.
ER -
KUDOVÁ, Jana, Ondřej VAŠÍČEK, Milan ČÍŽ a Lukáš KUBALA. Melatonin promotes cardiomyogenesis of embryonic stem cells via inhibition of HIF-1 alpha stabilization. \textit{JOURNAL OF PINEAL RESEARCH}. HOBOKEN: WILEY, 2016, roč.~61, č.~4, s.~493-503. ISSN~0742-3098. Dostupné z: https://dx.doi.org/10.1111/jpi.12366.
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