Melatonin promotes cardiomyogenesis of embryonic stem cells via inhibition of HIF-1α stabilization

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F16%3A00066010" target="_blank" >RIV/00159816:_____/16:00066010 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1111/jpi.12366" target="_blank" >http://dx.doi.org/10.1111/jpi.12366</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/jpi.12366" target="_blank" >10.1111/jpi.12366</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Melatonin promotes cardiomyogenesis of embryonic stem cells via inhibition of HIF-1α stabilization

Popis výsledku v původním jazyce

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 me- latonin inhibits the stabilization of hypoxia- inducible factors (HIFs), important sign- aling 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- 1α stabilization and transcriptional activity and, in con- trast, induced HIF- 2α stabilization. Interestingly, the deletion of HIF- 1α completely inhibited the pro- cardiomyogenic effect of melatonin as well as the melatonin- mediated HIF- 2α stabilization. Moreover, melatonin increased Sirt- 1 levels in a HIF- 1α- dependent manner. Taken together, we provide new evidence of a time- specific inhibition of HIF- 1α stabilization as an essential feature of melatonin- induced car- diomyogenesis and unexpected different roles of HIF- 1α 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.

Název v anglickém jazyce

Melatonin promotes cardiomyogenesis of embryonic stem cells via inhibition of HIF-1α stabilization

Popis výsledku anglicky

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 me- latonin inhibits the stabilization of hypoxia- inducible factors (HIFs), important sign- aling 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- 1α stabilization and transcriptional activity and, in con- trast, induced HIF- 2α stabilization. Interestingly, the deletion of HIF- 1α completely inhibited the pro- cardiomyogenic effect of melatonin as well as the melatonin- mediated HIF- 2α stabilization. Moreover, melatonin increased Sirt- 1 levels in a HIF- 1α- dependent manner. Taken together, we provide new evidence of a time- specific inhibition of HIF- 1α stabilization as an essential feature of melatonin- induced car- diomyogenesis and unexpected different roles of HIF- 1α 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.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FH - Neurologie, neurochirurgie, neurovědy

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Pineal Research

ISSN

0742-3098

e-ISSN

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Svazek periodika

61

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

493-503

Kód UT WoS článku

000386357100007

EID výsledku v databázi Scopus

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