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1.
J Physiol Biochem ; 75(4): 607-618, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31786730

RESUMO

Previous studies have shown that stromal interaction molecule1 (STIM1)-mediated store-operated Ca2+ entry (SOCE) contributes to intracellular Ca2+ accumulation in H9C2 cells subjected to hypoxia/reoxygenation(H/R) injury. The aim of the present study was to investigate the effect of resveratrol on STIM1-mediated intracellular Ca2+ accumulation and subsequent cell death in the context of myocardial ischemia/reperfusion (I/R) injury. C57 BL/6 mice were fed with either saline or resveratrol (50 mg/kg daily for 2 weeks) and then subjected to myocardial I/R injury. TTC/Evans Blue staining and TUNEL assay were performed to quantify the infarct size and apoptosis index. The cardiac function was evaluated by echocardiography. Neonatal rat ventricular cardiomyocytes (NRVCs) underwent hypoxia/reoxygenation (H/R) to establish the in vitro model. To achieve over-expression, NRVCs were transfected with STIM1-adenovirus vector. Apoptosis was analyzed by TUNEL assay. Cell viability was measured using MTS assay and cell necrosis was determined by LDH release assay. Intracellular Ca2+ concentration was detected by laser scanning confocal microscopy using a Fluo-3AM probe. Resveratrol significantly reduced apoptosis, decreased infarct size, and improved cardiac function in mice subjected to myocardial I/R injury. In NRVCs, resveratrol also downregulated STIM1 expression accompanied by decreased intracellular Ca2+ accumulation elicited by H/R injury. In addition, resveratrol reduced cell apoptosis, upregulated the Bcl-2, decreased Bax, and cleaved caspase-3 expression. Furthermore, the effects of resveratrol on STIM1-mediated intracellular Ca2+ accumulation, apoptotic proteins, and H/R-induced cell injury were exacerbated by STIM1 over-expression and were partly abolished by SOCE inhibitor SKF96365 in NRVCs in vitro. Our findings demonstrate that resveratrol exerts anti-apoptotic activity and improves cardiac functional recovery following myocardial I/R by inhibiting STIM1-induced intracellular Ca2+ accumulation.

2.
Chem Biol Interact ; 307: 82-90, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31047918

RESUMO

Honokiol (HKL) is a natural low-molecular-weight biphenolic compound derived from the bark of magnolia trees. Previous studies indicate that HKL exerts potent cardioprotective effects on ischemia/reperfusion (I/R) injury; however, evidence of the further relationship between HKL posttreatment and myocardial I/R injury has not been clearly found. In our study, we explored the protective effect of HKL post treatment on myocardial I/R injury in C57BL/6 mice. We also demonstrated that HKL significantly reduced cellular reactive oxygen species production and attenuated mitochondrial damage in neonatal rat cardiomyocytes exposed to hypoxia/reoxygenation (H/R). In addition, HKL was found to enhance autophagy during I/R or H/R; these effects could be partially blocked by the autophagic flux inhibitor chloroquine. Moreover, our results suggested that enhanced autophagic flux is associated with the Akt signaling pathway. Collectively, our results indicate that HKL posttreatment alleviates myocardial I/R injury and suggest a critical cardioprotective role of HKL in promoting autophagic flux.


Assuntos
Autofagia , Compostos de Bifenilo/uso terapêutico , Lignanas/uso terapêutico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Compostos de Bifenilo/química , Compostos de Bifenilo/farmacologia , Cloroquina/farmacologia , Modelos Animais de Doenças , Lignanas/química , Lignanas/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos
3.
Br J Pharmacol ; 176(17): 3126-3142, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31077347

RESUMO

BACKGROUND AND PURPOSE: Spermidine, a natural polyamine, is abundant in mammalian cells and is involved in cell growth, proliferation, and regeneration. Recently, oral spermidine supplements were cardioprotective in age-related cardiac dysfunction, through enhancing autophagic flux. However, the effect of spermidine on myocardial injury and cardiac dysfunction following myocardial infarction (MI) remains unknown. EXPERIMENTAL APPROACH: We determined the effects of spermidine in a model of MI, Sprague-Dawley rats with permanent ligation of the left anterior descending artery, and in cultured neonatal rat cardiomyocytes (NRCs) exposed to angiotensin II (Ang II). Cardiac function in vivo was assessed with echocardiography. In vivo and in vitro studies used histological and immunohistochemical techniques, along with western blots. KEY RESULTS: Spermidine improved cardiomyocyte viability and decreased cell necrosis in NRCs treated with angiotensin II. In rats post-MI, spermidine reduced infarct size, improved cardiac function, and attenuated myocardial hypertrophy. Spermidine also suppressed the oxidative damage and inflammatory cytokines induced by MI. Moreover, spermidine enhanced autophagic flux and decreased apoptosis both in vitro and in vivo. The protective effects of spermidine on cardiomyocyte apoptosis and cardiac dysfunction were abolished by the autophagy inhibitor chloroquine, indicating that spermidine exerted cardioprotective effects at least partly through promoting autophagic flux, by activating the AMPK/mTOR signalling pathway. CONCLUSIONS AND IMPLICATIONS: Our findings suggest that spermidine improved MI-induced cardiac dysfunction by promoting AMPK/mTOR-mediated autophagic flux.

4.
Life Sci ; 219: 231-237, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30630005

RESUMO

It is widely recognized that inadequate sleep is associated with multiple acute and chronic diseases and results in increased mortality and morbidity for cardiovascular diseases. In recent years, there has been increasing interest in sleep related investigations. Emerging evidence indicates that sleep deprivation changes the biological phenotypes of DNA, RNA and protein levels, but the underlying mechanisms are not clear. We summarized the current research on the detrimental roles of sleep deprivation on the heart and elucidated the underlying mechanisms of sleep deficiency to improve our understanding of sleep deprivation and the emerging strategies to target this process for therapeutic benefit.


Assuntos
Doenças Cardiovasculares/etiologia , Privação do Sono/complicações , Animais , Doenças Cardiovasculares/metabolismo , Humanos , Privação do Sono/metabolismo
5.
Biochem Biophys Res Commun ; 503(4): 2421-2428, 2018 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-29969626

RESUMO

Gastrodin (GAS), a monomeric component exacted from the herb Gastrodia elata Bl, may have cardioprotective effects during injury caused by myocardial ischemia/reperfusion (I/R). For the significant role of autophagy in I/R process, we targeted to explore whether autophagy was contributing to the GAS-induced protective effects during I/R procedure. Male C57BL/6 mice were subjected to reversible left coronary artery ligation and cultured neonatal rat cardiomyocytes (NRCs) exposed to hypoxia were preconditioned with GAS prior to ischemia or hypoxia, following reperfusion for 2 h or re-oxygennation for 3 h respectively. Our results demonstrated that GAS pretreatment increased autophagy and reduced apoptosis during I/R, this effect was weakened by co-treatment with the autophagic flux inhibitor chloroquine (Cq). Compared to mice subjected solely to I/R, GAS-pretreated mice had a notably smaller heart infarct size and an elevation in cardiac function. In GAS-pretreated NRCs, WB data showed that autophagy was promoted (expression of p62 was inhibited and LC3II was increased). In addition, tandem fluorescent mRFP-GFP-LC3 assays illustrated that autophagosomes were degraded duo to an increase in autophagic flux. Co-administration of Cq blocked the autophagic flux. Furthermore, GAS pretreatment increased the mitochondrial membrane potential of NRCs with subjected to H/R and increased the cardiomyocyte survival rate. These protective effects were reversed with Cq. Besides, GAS-induced the enhaucement of autophagy may correlated with activating AMP-activated protein kinase (AMPK) phosphorylation and reduced Mammalian target of rapamycin (mTOR) phosphorylation, which was abrogated by Compound C (Com C, AMPK-specific inhibitor). Our results establish that GAS pretreatment attenuates myocardial I/R injury by increasing autophagic flux aimed at eliminating dysfunctional mitochondria, therefore protecting neighbouring mitochondria and cardiomyocytes.


Assuntos
Autofagia/efeitos dos fármacos , Álcoois Benzílicos/uso terapêutico , Cardiotônicos/uso terapêutico , Glucosídeos/uso terapêutico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Álcoois Benzílicos/química , Cardiotônicos/química , Células Cultivadas , Gastrodia/química , Glucosídeos/química , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Fosforilação/efeitos dos fármacos , Proteínas Quinases/metabolismo , Ratos , Serina-Treonina Quinases TOR/metabolismo
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