SIRT1 is Required for Exercise-Induced Beneficial Effects on Myocardial Ischemia/Reperfusion Injury

Abstract

Background Exercise training has been regarded as an effective mean of prevention and treatment of cardiovascular diseases (CVD), and exercise can improve the antioxidant capacity of the myocardial. While SIRT1 has been proved to protects the heart from myocardial ischemia/reperfusion (MI/R) injury and apoptosis, less is known about the association between exercise-induced cardioprotection and SIRT1. Methods and Results MI/R injury model was constructed after swimming training in mice. Significantly reduced myocardial infarct size, decreased apoptosis ratio and upregulated SIRT1 protein expression in heart were found in swam mice by 2,3,5-triphenyltetrazolium chloride (TTC) staining of heart sections, TUNEL staining of frozen sections and Western blotting. The results of TUNEL staining and Western blotting suggested activation of SIRT1 using resveratrol (RSV) or inhibition of SIRT1 using EX527 in vitro blocked or accelerated cardiomyocytes apoptosis which induced by hypoxia/reoxygenation (H/R) respectively and regulated the expression of antioxidants in vitro. PGC-1α has been identified as one of the downstream genes of SIRT1 modulating oxidative stress and apoptosis. Importantly, the data of TTC staining, TUNEL staining, Western blotting, echocardiography and histopathological staining revealed that mice with inducible cardiac SIRT1-knockout blocked the protective effects of exercise preconditioning on myocardial infarct size, myocardial apoptosis, adverse ventricular remodeling, cardiac fibrosis and cardiac dysfunction after MI/R injury, simultaneously exercise-induced expression of myocardial antioxidant stress factors was hindered which was detected by immunohistochemical analysis. Conclusion SIRT1 protects against oxidative stress after MI/R injury by activating downstream PGC-1α and promoting the production of antioxidant enzymes. SIRT1 is required for exercise to protect against myocardial apoptosis and maladaptive ventricular remodelling induced by myocardial ischemia/reperfusion injury.

Resveratrol, novel application by preconditioning to attenuate myocardial ischemia/reperfusion injury in mice through regulate AMPK pathway and autophagy level

“…(4) To explore the effect of AMPK, SIRT1 in alleviating H/R damage, NRVMs were treated with 20 μM AMPK inhibitor (Compound C), or 10 μM SIRT1 inhibitor (EX‐527) at the beginning of reoxygenation, respectively. The dose was chosen according to previous studies 27,28 …”

“…The dose was chosen according to previous studies. 27,28 H9c2 cells were seeded at a density of 1 × 10 4 /cm 2 and cultured at DMEM containing 10% FBS with antibiotics in a cell incubator (humidified, 95% mixed air, 5% CO 2 , 37°C).…”

Molecular-Signaling Pathways of Ginsenosides Rb in Myocardial Ischemia-Reperfusion Injury: A Mini Review

“…Other than that, stimulation of the peroxisome proliferator-activated receptors gamma co-activator-1 alpha (PGC-1α) activities by SIRT1 is another potential mechanism related to cardioprotective effects via the SIRT1 pathway [55]. In a study conducted by Wang, Cao [55], SIRT1 deletion significantly attenuate the expression of PGC-1α, an essential transcription factor for many genes, including nuclear factor erythroid 2-related factor 2 (Nrf2). Subsequently, the expression of antioxidants enzymes SOD and heme-oxygenase 1 (HO-1) reduced, contributing to oxidative stress and eventually cell death [55].…”

“…In a study conducted by Wang, Cao [55], SIRT1 deletion significantly attenuate the expression of PGC-1α, an essential transcription factor for many genes, including nuclear factor erythroid 2-related factor 2 (Nrf2). Subsequently, the expression of antioxidants enzymes SOD and heme-oxygenase 1 (HO-1) reduced, contributing to oxidative stress and eventually cell death [55].…”

Combined Ketogenic Diet and Walking Exercise Interventions in Community Older Groups

“…catalase [87,88], glutamine synthetase [89] that these compounds cause older lifestyle changes like you know, people talk about exercising and walking that 3).…”