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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F16%3A00471949" target="_blank" >RIV/68081707:_____/16:00471949 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14310/16:00097518

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-1 alpha 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 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.

Název v anglickém jazyce

Melatonin promotes cardiomyogenesis of embryonic stem cells via inhibition of HIF-1 alpha 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 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.

Druh

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

CEP obor

BO - Biofyzika

OECD FORD obor

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Projekt

<a href="/cs/project/LD14030" target="_blank" >LD14030: Molekulární mechanismy interakcí serotoninergního systému s buňkami imunitního systému</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

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

—

Svazek periodika

61

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

DK - Dánské království

Počet stran výsledku

11

Strana od-do

493-503

Kód UT WoS článku

000386357100007

EID výsledku v databázi Scopus

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