RTA 408 ameliorates diabetic cardiomyopathy by activating Nrf2 to regulate mitochondrial fission and fusion and inhibiting NF-κB-mediated inflammation
Jinjin Hao, Jiedong Zhou, Songqing Hu, Peipei Zhang, Haowei Wu, Juntao Yang, Bingjie Zhao, Hanxuan Liu, Hui Lin, Jufang Chi, Da-jun Lou
Abstract
We demonstrated first that the nuclear factor erythroid 2-related factor 2 (Nrf2) activator RTA 408 has a protective effect against diabetic cardiomyopathy. We found that RTA 408 could stimulate the nuclear entry of Nrf2 protein, regulate the mitochondrial fission-fusion balance, and redistribute p65, which significantly alleviated the oxidative stress level in cardiomyocytes, thereby reducing apoptosis and inflammation, and protecting the systolic and diastolic functions of the heart.
Topics & Concepts
Diabetic cardiomyopathyInflammationOxidative stressActivator (genetics)Mitochondrial fissionApoptosisMedicinemitochondrial fusionCell biologyFusion proteinCardiomyopathyMitochondrionInternal medicineHeart failureChemistryBiologyMitochondrial DNAGeneReceptorBiochemistryRecombinant DNAGenomics, phytochemicals, and oxidative stressAdipose Tissue and MetabolismCardiovascular Function and Risk Factors