Exercise Mediated Nrf2 Signaling Protects the Myocardium From Isoproterenol-Induced Pathological Remodeling

Frontiers in Cardiovascular Medicine

Prasanna Krishnamurthy¹  Anil K. Challa¹  Gobinath Shanmugam²  Silvio H. Litovsky²  Christopher J. Davidson²  Asokan Devarajan³  Baskaran Athmanathan⁵  Namakkal Soorappan Rajasekaran⁶ 

[1] Redox Signaling Laboratory, Division of Molecular and Cellular Pathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, United States;;Cardiac Aging &Department of Biology, University of Alabama at Birmingham, Birmingham, AL, United States;Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, United States;Department of Medicine, Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States;Division of Cardiovascular Medicine, Department of Medicine, University of Utah, Salt Lake City, UT, United States;

关键词: antioxidants;    cardiac remodeling;    exercise;    echocardiography;    isoproterenol;    Nrf2;   

DOI  :  10.3389/fcvm.2019.00068

来源: DOAJ

【 摘 要 】

Although exercise derived activation of Nrf2 signaling augments myocardial antioxidant signaling, the molecular mechanisms underlying the benefits of moderate exercise training (MET) in the heart remain elusive. Here we hypothesized that exercise training stabilizes Nrf2-dependent antioxidant signaling, which then protects the myocardium from isoproterenol-induced damage. The present study assessed the effects of 6 weeks of MET on the Nrf2/antioxidant function, glutathione redox state, and injury in the myocardium of C57/BL6J mice that received isoproterenol (ISO; 50 mg/kg/day for 7 days). ISO administration significantly reduced the Nrf2 promoter activity (p < 0.05) and downregulated the expression of cardiac antioxidant genes (Gclc, Nqo1, Cat, Gsr, and Gst-μ) in the untrained (UNT) mice. Furthermore, increased oxidative stress with severe myocardial injury was evident in UNT+ISO when compared to UNT mice receiving PBS under basal condition. Of note, MET stabilized the Nrf2-promoter activity and upheld the expression of Nrf2-dependent antioxidant genes in animals receiving ISO, and attenuated the oxidative stress-induced myocardial damage. Echocardiography analysis revealed impaired diastolic ventricular function in UNT+ISO mice, but this was partially normalized in the MET animals. Interestingly, while there was a marginal reduction in ubiquitinated proteins in MET mice that received ISO, the pathological signs were attenuated along with near normal cardiac function in response to exercise training. Thus, moderate intensity exercise training conferred protection against ISO-induced myocardial injury by augmentation of Nrf2-antioxidant signaling and attenuation of isoproterenol-induced oxidative stress.

【 授权许可】

Unknown