RTA 408 ameliorates diabetic cardiomyopathy by activating Nrf2 to regulate mitochondrial fission and fusion and inhibiting NF-κB-mediated inflammation

Author:

Hao Jinjin1,Zhou Jiedong2,Hu Songqing3,Zhang Peipei4,Wu Haowei3,Yang Juntao2,Zhao Bingjie2,Liu Hanxuan2,Lin Hui5ORCID,Chi Jufang6ORCID,Lou Dajun1ORCID

Affiliation:

1. Department of Endocrinology, Shaoxing People’s Hospital, Shaoxing, China

2. College of Medicine, Shaoxing University, Shaoxing, China

3. Zhejiang University School of Medicine, Hangzhou, China

4. Zhejiang Chinese Medical University, Hangzhou, China

5. The Affiliated Lihuili Hospital of Ningbo University, Ningbo, China

6. Department of Cardiology, Zhuji People’s Hospital, Shaoxing, China

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.

Funder

Object of Training High-level Innovative Health Talents in Zhejiang Province

MOST | National Natural Science Foundation of China

Publisher

American Physiological Society

Subject

Cell Biology,Physiology

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