期刊
FASEB JOURNAL
卷 36, 期 9, 页码 -出版社
WILEY
DOI: 10.1096/fj.202200543RRR
关键词
curcumin; diabetic cardiomyopathy; hyperglycemia; Nrf2; HO-1 signaling; reactive oxygen species
资金
- National Natural Science Foundation of China (NSFC) [81860054, 81570262]
- Natural Science Foundation of Jiangxi Province (Jiangxi Province natural Science Fund) [700207006]
This study reveals the mechanism of diabetic cardiomyopathy and finds that high glucose leads to excessive ROS production, inhibiting the activation of the Nrf2 signaling pathway, resulting in decreased cardiac energy metabolism and increased cell apoptosis. Additionally, it is discovered that activation of the Nrf2 signaling pathway can reduce ROS formation, increase antioxidant enzyme activity, and inhibit cardiomyocyte apoptosis.
The hallmark feature of Diabetes mellitus (DM) is hyperglycemia which can lead to excess production of reactive oxygen species (ROS) in the myocardium, contributing to diabetic cardiomyopathy (DCM). Nuclear factor erythroid2-related factor2 (Nrf2), a transcriptional activator, enhances its ability to resist oxidative stress by activating multiple downstream anti-oxidants, anti-inflammatory proteins, and detoxifying enzymes. However, the mechanism of Nrf2 signaling in HG-induced DCM is unclear. In this study, we used HG pretreated H9c2 cells as the experimental basis in vitro, and established a high fat-diet, streptozotocin (STZ) induced Type 2 diabetic rat model in vivo. Meanwhile, we used shRNA-Nrf2 and curcumin (CUR) (as an activator) to affect H9c2 cells, to verify the role of the Nrf2 signaling pathway in DCM. The results showed that the excessive production of ROS caused by HG, which could inhibit the activation of Nrf2-related signaling, resulting in a decrease in cell energy metabolism and an increase in cell apoptosis. Surprisingly, we found that the activation of the Nrf2 signaling pathway significantly increased cardiomyocyte viability, reduced ROS formation, increased antioxidant enzyme activity, and inhibited cardiomyocyte apoptosis. In conclusion, these findings conclusively infer that CUR activation of the Nrf2/HO-1 signaling pathway exerts myocardial protection by reducing ROS formation.
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