Melatonin upregulates DNA-PKcs to suppress apoptosis of human umbilical vein endothelial cells via inhibiting miR-101 under HO-induced oxidative stress.

Melatonin has been implicated in inhibiting oxidative stress-induced apoptosis of endothelial cells. However, the underlying mechanism remains poorly understood. In this study, we examined the effect of melatonin on apoptosis of human umbilical vein endothelial cells (HUVECs) induced by HO and explored the underlying mechanisms. Our results demonstrated that DNA-dependent protein kinase catalytic subunit (DNA-PKcs) upregulation contributed to the protective role of melatonin in HUVECs under oxidative stress with HO. Further study showed that melatonin treatment led to a decreased level of miRNA-101, which could be responsible for DNA-PKcs upregulation and DNA-PKcs-mediated apoptosis inhibition in HUVECs under oxidative stress with HO. Our results also showed that melatonin increased the activity of PI3K/AKT and DNA-PKcs knockdown in melatonin-treated HUVECs that lead to inactivation of PI3K/AKT signaling under oxidative stress with HO. Furthermore, blockade of PI3K/AKT signal with LY294002 significantly reduced melatonin-induced apoptosis inhibition in HO-treated HUVECs. Taken together, our findings identify a miR-101/DNA-PKcs/PI3K/AKT signaling pathway in melatonin-induced endothelial cell apoptosis inhibition under oxidative stress with HO.