Abstract 458: Moderate Exercise Training Attenuates Isoproterenol-Induced Myocardial Injury by Activating Nrf2-Signaling

Autor: Gobinath Shanmugam, Madhusudhanan Narasimhan, Robbie Conley, Rajesh Kumar Radhakrishnan, Silvio H Litovsky, Namakkal-Soorapppan Rajasekaran
Rok vydání: 2017
Předmět:
Zdroj: Circulation Research. 121
ISSN: 1524-4571
0009-7330
DOI: 10.1161/res.121.suppl_1.458
Popis: Background: Nuclear erythroid-2 like factor-2 (Nrf2), a master transcriptional regulator of antioxidants, is critical to maintain cellular redox homeostasis. We recently reported that exercise training activates Nrf2/antioxidant signaling in the heart. Isoproterenol (ISO) mediated structural, and functional changes in the heart involve oxidative stress. Here, we tested a hypothesis that moderate exercise training will protect the myocardium from isoproterenol-induced injury by augmenting Nrf2-dependent antioxidant defense system. Methods: Age- and sex-matched WT (C57/BL6) mice (6-8 months old) were subjected to moderate exercise training (MET) on a treadmill for 6 weeks (60 min/day; 10m/min; 0% grade). Randomly assigned untrained (UNT) and trained (MET) animals were intraperitoneally injected (at the start of 6 th week) with 50 mg of isoproterenol/kg.bw./day for 7 consecutive days. MET was continued during ISO administration and the animals (UNT + PBS, UNT + ISO; MET + ISO) underwent echocardiography analysis. Heart tissues were collected for histopathology, Nrf2-ARE promoter binding assay (Active-motif TransAM kit), antioxidant gene (qPCR) and protein (Immunoblotting) levels, and glutathione redox status. Results: ISO administration significantly reduced the Nrf2 promoter activity (pGclc, Nqo1, Cat, Gsr and Gst-μ ) in UNT mice. Further, increased oxidative stress with severe myocardial injury was evident in UNT+ISO when compared to UNT mice receiving PBS under basal condition. Interestingly, MET stabilized the Nrf2-promoter activity and promoted the expression of Nrf2-dependent antioxidant genes and proteins animals receiving ISO, and thereby attenuated the oxidative stress-induced myocardial damage. Echocardiography analysis showed impaired systolic/diastolic ventricular volumes coupled with decreased cardiac output in UNT+ISO mice, but this was normalized in exercise-trained animals. Conclusion: Thus moderate exercise training conferred protection against ISO-induced myocardial injury by augmentation of Nrf2-antioxidant signaling and attenuation of redox perturbations.
Databáze: OpenAIRE
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