Notch1–Nrf2 signaling crosstalk provides myocardial protection by reducing ROS formation
Xueliang Zhou, Xia Wu, Rongrong Zhu, Hua Xu, Yunyun Li, Qirong Xu, Sheng Liu, Songqing Lai, Xinping Xu, Li Wan, Qicai Wu, Jichun Liu
Abstract
Both the Notch1 and Keap1-Nrf2 signaling pathways have cardioprotective effects, but the role of Notch1-Nrf2 crosstalk in myocardial ischemia-reperfusion injury is unclear. In this study, we established hypoxia-reoxygenation in neonate rat myocardial cells and employed γ-secretase inhibitor and curcumin to inhibit and activate the Notch1 and Keap1-Nrf2 signaling pathways, respectively. We found that the combined action of the Notch1 and Keap1-Nrf2 signaling pathways significantly increased cardiomyocyte viability, inhibited cardiomyocyte apoptosis, reduced the formation of reactive oxygen species, and increased antioxidant activities. In conclusion, these findings suggest that Notch1-Nrf2 crosstalk exerts myocardial protection by reducing the formation of reactive oxygen species.