ISSN: 1449-2288International Journal of Biological Sciences
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Int J Biol Sci 2022; 18(4):1651-1662. doi:10.7150/ijbs.63297 This issue Cite
Research Paper
Keap-NRF2 signaling contributes to the Notch1 protected heart against ischemic reperfusion injury via regulating mitochondrial ROS generation and bioenergetics
1. Department of Cardiac Surgery, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330006, China.
2. Department of Electrocardiogram, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330006, China.
3. Department of Obstetrics and Gynecology, Gaoxin Hospital of the First Affiliated Hospital of Nanchang University, Nanchang, China.
4. Zhangjiang Institute, Fudan University, Shanghai, China.
# These authors contribute equally to this study
Abstract
Myocardial ischemia/reperfusion (I/R) injury is recognized as the leading cause of death worldwide. However, the molecular mechanisms involved in this process are still not fully understood. We previously reported that the combined action of Notch1 and Keap1-NRF2 signaling pathway can significantly increase the activity of cardiomyocytes, inhibit the apoptosis of cardiomyocytes, reduce the formation of reactive oxygen species, and improve the antioxidant activity in neonate rat myocardial cells. However, the regulatory mechanism of Notch1 signaling pathway on the NRF2 signaling pathway and its actual role on I/R injury are still unclear. Herein, we found that Keap-NRF2 signaling is activated by Notch1 in RBP-Jκ dependent manner, thus protects the heart against I/R injury via inhibiting the mitochondrial ROS generation and improves the mitochondrial bioenergetics in vitro and in vivo. These results suggest that Keap-NRF2 signaling might become a promising therapeutic strategy for treating myocardial I/R injury.
Keywords: NRF2, Notch1, mitochondrial ROS, mitochondrial bioenergetics, ischemic reperfusion injury
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