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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 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.
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