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

J 2016

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

KUDOVÁ, Jana, Ondřej VAŠÍČEK, Milan ČÍŽ and Lukáš KUBALA

Basic information

Original name

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

Authors

KUDOVÁ, Jana (203 Czech Republic, belonging to the institution), Ondřej VAŠÍČEK (203 Czech Republic, belonging to the institution), Milan ČÍŽ (203 Czech Republic, belonging to the institution) and Lukáš KUBALA (203 Czech Republic, guarantor, belonging to the institution)

Edition

JOURNAL OF PINEAL RESEARCH, HOBOKEN, WILEY, 2016, 0742-3098

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10601 Cell biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 10.391

RIV identification code

RIV/00216224:14310/16:00097518

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1111/jpi.12366

UT WoS

000386357100007

Keywords in English

cardiomyogenesis; hypoxia-inducible factor-alpha; melatonin; mouse embryonic stem cells

Abstract

V originále

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.

Citovat

KUDOVÁ, Jana, Ondřej VAŠÍČEK, Milan ČÍŽ and Lukáš KUBALA. Melatonin promotes cardiomyogenesis of embryonic stem cells via inhibition of HIF-1 alpha stabilization. JOURNAL OF PINEAL RESEARCH. HOBOKEN: WILEY, 2016, vol. 61, No 4, p. 493-503. ISSN 0742-3098. Available from: https://dx.doi.org/10.1111/jpi.12366.

@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 and Lukáš KUBALA. Melatonin promotes cardiomyogenesis of embryonic stem cells via inhibition of HIF-1 alpha stabilization. \textit{JOURNAL OF PINEAL RESEARCH}. HOBOKEN: WILEY, 2016, vol.~61, No~4, p.~493-503. ISSN~0742-3098. Available from: https://dx.doi.org/10.1111/jpi.12366.

Detailed Information on Publication Record