Informace o publikaci

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

Autoři

KUDOVÁ Jana VAŠÍČEK Ondřej ČÍŽ Milan KUBALA Lukáš

Rok publikování 2016
Druh Článek v odborném periodiku
Časopis / Zdroj JOURNAL OF PINEAL RESEARCH
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
Doi http://dx.doi.org/10.1111/jpi.12366
Klíčová slova cardiomyogenesis; hypoxia-inducible factor-alpha; melatonin; mouse embryonic stem cells
Popis 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.

Používáte starou verzi internetového prohlížeče. Doporučujeme aktualizovat Váš prohlížeč na nejnovější verzi.

Další info