Melatonin upregulates DNA-PKcs to suppress apoptosis of human umbilical vein endothelial cells via inhibiting miR-101 under H2O2-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 H2O2 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 H2O2. 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 H2O2. 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 H2O2. Furthermore, blockade of PI3K/AKT signal with LY294002 significantly reduced melatonin-induced apoptosis inhibition in H2O2-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 H2O2.

Automated summary

Melatonin was found to inhibit endothelial cell apoptosis under oxidative stress induced by H2O2 through modulation of the miR-101/DNA-PKcs/PI3K/AKT signaling pathway.