Sesamin Protects Against Cardiac Remodeling Via Sirt3/ROS Pathway

Fan, Di; Zheng, Yang; Liu, Fang-Yuan; Jin, Ya‐Ge; Zhang, Ning; Ni, Jian; Yuan, Yuan; Liao, Hai-Han; Wu, Qin; Xu, Man; Deng, Wei; Tang, Qi‐Zhu

doi:10.1159/000486026

Cited by 39 publications

(28 citation statements)

References 45 publications

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“…ISO treatment generates highly cytotoxic ROS, resulting in the peroxidation of membrane phospholipids, inducing marked impairment of the myocardial membrane associated with infarct-like necrosis of the heart muscle (44). Excessive ROS generation also activates various intracellular signaling pathways regulating myocyte survival, apoptosis and cardiac remodeling (45). Additionally, accumulating evidence suggests that Nox, the major source of ROS in the cardiovascular system, is an important downstream effector of the TGF-β signaling pathway, whereas Nox-dependent redox signaling regulates TGF-β/Smad signaling in a feedforward manner (46).…”

Section: Discussionmentioning

confidence: 99%

Growth differentiation factor 11 is involved in isoproterenol‑induced heart failure

et al. 2019

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The present study aimed to investigate the potential effects of growth differentiation factor 11 (GDF11) on isoproterenol (ISO)-induced heart failure (HF) and identify the underlying molecular mechanisms. A rat model of HF was induced in vivo by intraperitoneally administering ISO (5 mg/kg/day) for 7 days. After 4 weeks following establishment of the HF model, hemodynamic analysis demonstrated that ISO induced a significant increase in the left ventricular end-diastolic pressure and a decrease in the left ventricular systolic pressure and maximum contraction velocity. The plasma levels of myocardial injury markers, including lactate dehydrogenase (LDH), creatine kinase (CK), CK-muscle/brain which were determined using the corresponding assay kits and plasma brain natriuretic peptide which was detected by an ELISA kit, an important biomarker of HF, increased following ISO treatment. Furthermore, levels of GDF11 expression and protein, which were estimated using reverse transcription-quantitative polymerase chain reaction and an ELISA kit in plasma and western blotting in the heart tissue, respectively, significantly increased following ISO treatment. To demonstrate the effects of ISO on GDF11 production in cardiomyocytes, H9C2 cells (a cardiomyoblast cell line derived from embryonic rat heart tissue) were treated with ISO (50 nM) for 24 h in vitro ; it was revealed that GDF11 protein and mRNA expression levels significantly increased following ISO treatment. In addition, recombinant GDF11 (rGDF11) administered to ISO-treated H9C2 cells resulted in decreased proliferation, which was detected via a CCK-8 assay, and increased LDH levels and cell apoptosis of cells, which was determined using Caspase-3 activity and Hoechst 33258 staining. Additionally, rGDF11 increased the levels of reactive oxygen species and malondialdehyde due to the upregulation of nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) following rGDF11 treatment. Conversely, GDF11 knockdown reduced ISO-induced apoptosis by inhibiting oxidative stress injury. The results suggested that GDF11 production was upregulated in ISO-induced rats with HF and in ISO-treated H9C2 cells, and that rGDF11 treatment increased ISO-induced oxidative stress injury by upregulating Nox4 in H9C2 cells.

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Section: Discussionmentioning

confidence: 99%

Growth differentiation factor 11 is involved in isoproterenol‑induced heart failure

et al. 2019

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“…Sirtuins are highly conserved NAD + -dependent deacetylases involved in many cellular processes, including oxidative stress regulation, genomic stability maintaining, and DNA repair [ 41 , 42 ]. Deletion of SIRT3 promoted protein acetylation, cyclophilin D rearrangement, and mitochondrial permeability transition pore opening, thereby resulting in severe oxidative damage [ 43 ]. Low expression of SIRT3 resulted in myocardial NAD + depletion, mitochondrial enzyme acetylation, and heart failure, indicating that SIRT3 is pivotal for the maintenance of mitochondrial homeostasis [ 44 , 45 , 46 , 47 , 48 ].…”

Section: Discussionmentioning

confidence: 99%

Dihydromyricetin Attenuates Myocardial Hypertrophy Induced by Transverse Aortic Constriction via Oxidative Stress Inhibition and SIRT3 Pathway Enhancement

Chen

Luo

Sun

et al. 2018

IJMS

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Dihydromyricetin (DMY), one of the flavonoids in vine tea, exerts several pharmacological actions. However, it is not clear whether DMY has a protective effect on pressure overload-induced myocardial hypertrophy. In the present study, male C57BL/6 mice aging 8–10 weeks were subjected to transverse aortic constriction (TAC) surgery after 2 weeks of DMY (250 mg/kg/day) intragastric administration. DMY was given for another 2 weeks after surgery. Blood pressure, myocardial structure, cardiomyocyte cross-sectional area, cardiac function, and cardiac index were observed. The level of oxidative stress in the myocardium was assessed with dihydroethidium staining. Our results showed that DMY had no significant effect on the blood pressure. DMY decreased inter ventricular septum and left ventricular posterior wall thickness, relative wall thickness, cardiomyocyte cross-sectional areas, as well as cardiac index after TAC. DMY pretreatment also significantly reduced arterial natriuretic peptide (ANP), brain natriuretic peptide (BNP) mRNA and protein expressions, decreased reactive oxygen species production and malondialdehyde (MDA) level, while increased total antioxidant capacity (T-AOC), activity of superoxide dismutase (SOD), expression of sirtuin 3 (SIRT3), forkhead-box-protein 3a (FOXO3a) and SOD2, and SIRT3 activity in the myocardium of mice after TAC. Taken together, DMY ameliorated TAC induced myocardial hypertrophy in mice related to oxidative stress inhibition and SIRT3 pathway enhancement.

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“…ROS production was evaluated by DHE staining in vivo and DCFH-DA staining in vitro [38,40]. Briefly, cryosections of fresh heart samples or coverslips were stained with DHE (5 μmol/L) or DCFH-DA (5 μmol/L) in the dark at 37°C for 30 min, and then were visualized in a blinded manner under an Olympus IX53fluorescence microscope.…”

Section: Oxidative Stress Detection and Cell Viabilitymentioning

confidence: 99%

FNDC5 alleviates oxidative stress and cardiomyocyte apoptosis in doxorubicin-induced cardiotoxicity via activating AKT

et al. 2019

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Oxidative stress and cardiomyocyte apoptosis play critical roles in doxorubicin (DOX)-induced cardiotoxicity. Previous studies indicated that fibronectin type III domain-containing 5 (FNDC5) and its cleaved form, irisin, could preserve mitochondrial function and attenuate oxidative damage as well as cell apoptosis, however, its role in DOX-induced cardiotoxicity remains unknown. Our present study aimed to investigate the role and underlying mechanism of FNDC5 on oxidative stress and cardiomyocyte apoptosis in DOX-induced cardiotoxicity. Cardiomyocyte-specific FNDC5 overexpression was achieved using an adeno-associated virus system, and then the mice were exposed to a single intraperitoneal injection of DOX (15 mg/kg) to generate DOX-induced cardiotoxicity. Herein, we found that FNDC5 expression was downregulated in DOX-treated murine hearts and cardiomyocytes. Fndc5 deficiency resulted in increased oxidative damage and apoptosis in H9C2 cells under basal conditions, imitating the phenotype of DOX-induced cardiomyopathy in vitro, conversely, FNDC5 overexpression or irisin treatment alleviated DOX-induced oxidative stress and cardiomyocyte apoptosis in vivo and in vitro. Mechanistically, we identified that FNDC5/Irisin activated AKT/mTOR signaling and decreased DOX-induced cardiomyocyte apoptosis, and moreover, we provided direct evidence that the anti-oxidant effect of FNDC5/Irisin was mediated by the AKT/GSK3β/FYN/Nrf2 axis in an mTOR-independent manner. And we also demonstrated that heat shock protein 20 was responsible for the activation of AKT caused by FNDC5/Irisin. In line with the data in acute model, we also found that FNDC5/Irisin exerted beneficial effects in chronic model of DOX-induced cardiotoxicity (5 mg/kg, i.p., once a week for three times, the total cumulative dose is 15 mg/kg) in mice. Based on these findings, we supposed that FNDC5/Irisin was a potential therapeutic agent against DOX-induced cardiotoxicity.

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Sesamin Protects Against Cardiac Remodeling Via Sirt3/ROS Pathway

Cited by 39 publications

References 45 publications

Growth differentiation factor 11 is involved in isoproterenol‑induced heart failure

Growth differentiation factor 11 is involved in isoproterenol‑induced heart failure

Dihydromyricetin Attenuates Myocardial Hypertrophy Induced by Transverse Aortic Constriction via Oxidative Stress Inhibition and SIRT3 Pathway Enhancement

FNDC5 alleviates oxidative stress and cardiomyocyte apoptosis in doxorubicin-induced cardiotoxicity via activating AKT

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