Endocrine Abstracts

Hypoxia causes oxidative stress and is known to affect cardiovascular dysfunction and the programming of cardiovascular disease. Melatonin is the hormone released primarily from the pineal gland and has been proven to be an antioxidant. Melatonin promotes the expression of antioxidant enzymes such as superoxide dismutase and catalase. To confirm the effect of hypoxia on the differentiation of mouse embryonic stem cells (mESCs) into cardiomyocytes, hypoxia condition induced during the differentiation period. mRNA expressions of cardiac-lineage markers (Brachyury, Tbx20, and Ctn1) decreased at differentiation 2-10day. The expression of hypoxia marker, Hif-1α, was increased in the hypoxia condition-plus mESC differentiation 2–10, 6–10, and 2–10 day, but melatonin receptor -Mtnr1a mRNA expression was reduced in the hypoxia condition-plus mESC differentiation 6–10 and 2–10 day. To confirm the effect of melatonin against the hypoxia condition, melatonin was treated. Beating ratio and the mRNA expression of cardiac-specific marker (Ctn1) restored in 500 µM melatonin-plus hypoxia condition. The level of Hif-1α protein decreased in melatonin (100, 500 µM)-plus hypoxia, but the Mtnr1a mRNA expression was increased. In these conditions, the expressions of p-ERK and Bax proteins decreased, but the levels of p-Akt, PI3k, and Bcl-2 proteins increased. Melatonin has been shown to mitigate hypoxia via the ERK pathway in the differentiation of mESCs into cardiomyocytes. The expression of Mtnr1a mRNA was increased during the differentiation of mouse stem cells into cardiomyocytes, indicating that melatonin may affect cardiomyocyte differentiation. These results suggest that melatonin may protect against hypoxia in cardiomyocyte differentiation of mouse embryonic stem cells.