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Cardiomyocytes and mToR

Ru-Li Li, Si-Si Wu, Yao Wu, Xiao-Xiao Wang, Hong-Ying Chen, Juan-Juan Xin, He Li, Jie Lan, Kun-Yue Xue, Xue Li, Cai-Li Zhuo, Yu-Yan Cai, Jin-Han He, Heng-Yu Zhang, Chao-Shu Tang, Wang Wang, Wei Jiang
In hypertrophic hearts, autophagic flux insufficiency is recognized as a key pathology leading to maladaptive cardiac remodeling and heart failure. This study aimed to illuminate the cardioprotective role and mechanisms of a new myokine and adipokine, irisin, in cardiac hypertrophy and remodeling. Adult male wild-type, mouse-FNDC5 (irisin-precursor)-knockout and FNDC5 transgenic mice received 4 weeks of transverse aortic constriction (TAC) alone or combined with intraperitoneal injection of chloroquine diphosphate (CQ)...
July 24, 2018: Journal of Molecular and Cellular Cardiology
Dan Shao, Outi Villet, Zhen Zhang, Sung Won Choi, Jie Yan, Julia Ritterhoff, Haiwei Gu, Danijel Djukovic, Danos Christodoulou, Stephen C Kolwicz, Daniel Raftery, Rong Tian
Glucose and branched-chain amino acids (BCAAs) are essential nutrients and key determinants of cell growth and stress responses. High BCAA level inhibits glucose metabolism but reciprocal regulation of BCAA metabolism by glucose has not been demonstrated. Here we show that glucose suppresses BCAA catabolism in cardiomyocytes to promote hypertrophic response. High glucose inhibits CREB stimulated KLF15 transcription resulting in downregulation of enzymes in the BCAA catabolism pathway. Accumulation of BCAA through the glucose-KLF15-BCAA degradation axis is required for the activation of mTOR signaling during the hypertrophic growth of cardiomyocytes...
July 26, 2018: Nature Communications
Chengxi Zhang, Sinian Pan, Ayipaxa Aisha, Minawaer Abudoukelimu, Leile Tang, Yesheng Ling
This study aimed to investigate whether recombinant human brain natriuretic peptide (rhBNP) regulated hypoxia-induced injury in H9c2 cardiomyocytes through lncRNA EGOT. H9c2 cardiomyocytes were cultured under normoxia and hypoxia (21% and 3% O2 ) conditions, and whether hypoxia induced injury by assessing cell viability, apoptosis and autophagy. H9c2 cells were then treated with different doses of exogenous rhBNP (200, 600 and 900 nmol/L, respectively) and the effects of rhBNP on hypoxia-induced injury in H9c2 cells as well as the expression of EGOT were studied...
July 18, 2018: Biochemical and Biophysical Research Communications
Asli F Ceylan, Shuyi Wang, Machender R Kandadi, Jie Chen, Yinan Hua, Zhaohui Pei, Sreejayan Nair, Jun Ren
Endothelin (ET)-1 is implicated in the pathophysiology of cardiovascular diseases although its role in obesity anomalies has not been fully elucidated. This study was designed to examine the impact of ET-1 receptor A (ETA ) ablation on obesity-induced changes in cardiac geometry and contractile function, as well as the mechanisms involved with a focus on autophagy. Cardiomyocyte-specific ETA receptor knockout (ETAKO) and WT mice were fed either low-fat (10% calorie from fat) or high-fat (45% calorie from fat) diet for 24 weeks...
July 18, 2018: Biochimica et Biophysica Acta
Yao Qing, Xu Dong, Li Hongli, Liu Yanhui
BACKGROUND: Berberine has been verified to protect the heart from ischemia/reperfusion injury through animal experiments. However, the cardioprotective properties of berberine have not been established fully. This study was aimed at investigating whether berberine is cardioprotective in vivo and in vitro. METHODS: In the cardiomyoblast cells, the autophagosomes were observed by immunostaining. The apoptosis was detected by a flow cytometry. Beclin-1, LC3-II/I, adenosine monophosphate-activated protein kinase (AMPK), and mTOR in cardiomyocytes were detected by Western blot...
September 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Ying Luo, Zhiqiang Sun, Pengfei Hu, Yuanhong Wu, Weiwei Yu, Shuwei Huang
Objective: Descurainia sophia (L.) Webb ex Prantl (DS) is a traditional Chinese medicine. Our current study was to evaluate the effect of DS on ventricular remodeling in chronic heart failure (HF) rats and its underlying mechanism. Methods: The rat chronic heart failure model induced by suprarenal abdominal aortic coarctation surgery. The survival rats were randomly divided into 3 groups: the sham group (n=6), the HF group (n=6), and the HF+DS group (n=6). After 3 months of drug intervention, we examined the effects of DS by Sirius Red staining, electron microscopy, echocardiography, hemodynamic measurement, and TUNEL and explored the underlying mechanism by Western blotting...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
Nicola Manzella, Yohan Santin, Damien Maggiorani, Hélène Martini, Victorine Douin-Echinard, Joao F Passos, Frank Lezoualc'h, Claudia Binda, Angelo Parini, Jeanne Mialet-Perez
Cellular senescence, the irreversible cell cycle arrest observed in somatic cells, is an important driver of age-associated diseases. Mitochondria have been implicated in the process of senescence, primarily because they are both sources and targets of reactive oxygen species (ROS). In the heart, oxidative stress contributes to pathological cardiac ageing, but the mechanisms underlying ROS production are still not completely understood. The mitochondrial enzyme monoamine oxidase-A (MAO-A) is a relevant source of ROS in the heart through the formation of H2 O2 derived from the degradation of its main substrates, norepinephrine (NE) and serotonin...
July 12, 2018: Aging Cell
Wenliang Zhong, Wen Jin, Shanghua Xu, Yanqing Wu, Shunxiang Luo, Minlie Liang, Lianglong Chen
BACKGROUND: Pioglitazone has been widely used as an insulin-sensitizing agent for improving glycemic control in patients with type 2 diabetes mellitus. However, cardiovascular risk and protective effects of pioglitazone remain controversial. OBJECTIVES: In this study, we investigated whether pioglitazone affects cardiomyocyte apoptosis and hypertrophy by regulating the VEGFR-2 signaling pathway. METHODS: Cardiomyocytes were enzymatically isolated from 1- to 3-day-old Sprague-Dawley rat ventricles...
July 2, 2018: Arquivos Brasileiros de Cardiologia
Shanshan Fu, Linlin Chen, Yizhang Wu, Ying Tang, Lu Tang, Yongkang Zhong, Siyi Wang, Haiqiong Liu, Xianbao Wang, Aihua Chen
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...
July 3, 2018: Biochemical and Biophysical Research Communications
Jung Hyun Park, Hyeong Jun Ku, Jae Kyeom Kim, Jeen-Woo Park, Jin Hyup Lee
Heart failure is a frequent unfavorable outcome of pathological cardiac hypertrophy. Recent increase in dietary fructose consumption mirrors the rise in prevalence of cardiovascular diseases such as cardiac hypertrophy leading to concerns raised by public health experts. Mitochondria, comprising 30% of cardiomyocyte volume, play a central role in modulating redox-dependent cellular processes such as metabolism and apoptosis. Furthermore, mitochondrial dysfunction is a key cause of pathogenesis of fructose-induced cardiac hypertrophy...
June 21, 2018: Scientific Reports
Liang Qin, Shuxia Fan, Rongbo Jia, Yongxuan Liu
AIM: Myocardial ischemia (MI) is a leading cause of morbidity and mortality which makes the prevention and control of MI tremendously important. We aimed to explore the functional roles of ginsenoside (Gin) Rg1 in cardiomyocytes under hypoxia and to clarify underlying mechanisms. MAIN METHODS: Hypoxia-induced H9c2 cell injury was evaluated by alterations of cell viability, apoptosis and autophagy. Then, effects of Gin Rg1 on hypoxia-induced cell injury were measured...
June 1, 2018: Die Pharmazie
Zhidan Chen, Yang Li, Guoliang Jiang, Chunjie Yang, Ying Wang, Xiang Wang, Bo Fang, Guoping Zhang, Yongxin Sun, Juying Qian, Hui Gong, Yunzeng Zou
Lipoprotein receptor-related protein 6 (LRP6) binds to Wnt ligands to transduce signal by stabilization of β-catenin, which has been involved in the regulation of embryonic development and metabolism et al. Here, we observed LRP6 decreased in human hearts with dilated cardiomyopathy (DCM), and it also decreased in cultured cardiomyocytes under glucose- deprivation (GD). Knockdown of LRP6 greatly inhibited cell viability in cardiomyocytes under GD, but it didn't induce the effect in cardiomyocytes at baseline...
July 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Wei Yu, Wenliang Zha, Jun Ren
Mitochondrial injury and defective autophagy are common in diabetic cardiomyopathy. Recent evidence supports benefits of glucagon-like peptide-1 (GLP-1) agonists exendin-4 (Exe) and liraglutide (LIRA) against diabetic cardiomyopathy. This study was designed to examine the effect of Exe and LIRA on glucose-induced cardiomyocyte and mitochondrial injury, oxidative stress, apoptosis, and autophagy change. Cardiomyocytes isolated from adult mice and H9c2 myoblast cells were exposed to high glucose (HG, 33 mM) with or without Exe or LIRA...
2018: Oxidative Medicine and Cellular Longevity
Yihui Yu, Zuoying Hu, Bing Li, Zhimei Wang, Shaoliang Chen
This study aimed to investigate the effects and molecular mechanisms of ivabradine in preventing cardiac hypertrophy in an established transverse aortic constriction (TAC) mouse model. A total of 56 male C57BL/6 mice were randomly assigned into the following seven groups (8 mice per group): sham, TAC model, Iva-10 (10 mg/kg/day ivabradine), Iva-20 (20 mg/kg/day ivabradine), Iva-40 (40 mg/kg/day ivabradine), Iva-80 (80 mg/kg/day ivabradine), and Rap (rapamycin, a positive control). Echocardiography and left ventricular hemodynamics were performed...
May 22, 2018: Molecular and Cellular Biochemistry
Chao Zhao, Yong Mei, Xufeng Chen, Lei Jiang, Yunfei Jiang, Xu Song, Hang Xiao, Jingsong Zhang, Jun Wang
Methamphetamine (METH) is a commonly abused psychostimulant that can induce severe neurotoxicity. Cardiovascular injury caused by METH has recently gained increasing attention; however, the underlying mechanisms remain unclear. As autophagy has been shown to be associated with cell injury, the association between autophagy and METH-mediated cell apoptosis was investigated in the present study. METH treatment significantly increased the expression of two key autophagy proteins, i.e., Beclin-1 and LC3-II, in the cardiomyocyte cell line H9C2...
September 15, 2018: Toxicology Letters
Xuan Ke, Yanqin Hao, Bingong Li, Jin Zou, Xuelian Li, Chunying Wei, Fuyou Liu, Zhiyong Zhang
Visceral adipose tissue-derived serine protease inhibitor (Vaspin) is an adipocytokine that has been shown to exert anti-inflammatory effects and inhibits apoptosis under diabetic conditions. This study was designed to investigate the impact of vaspin on autophagy in tumor necrosis factor (TNF)-α-induced injury in cardiomyocytes and its cardioprotective effects in the pathogenesis of diabetic cardiomyopathy (DCM). H9C2 cells were treated with TNF-α with or without vaspin in vitro. Tumor necrosis factor-α treatment inhibited autophagy and promoted apoptosis in H9C2 cells after stimulating for 24 hours...
May 2018: Journal of Cardiovascular Pharmacology
Leiming Wu, Lu Gao, Dianhong Zhang, Rui Yao, Zhen Huang, Binbin Du, Zheng Wang, Lili Xiao, Pengcheng Li, Yapeng Li, Cui Liang, Yanzhou Zhang
RATIONALE: Complement C1q tumor necrosis factor related proteins (C1QTNFs) have been reported to have diverse biological influence on the cardiovascular system. C1QTNF1 is a member of the CTRP superfamily. C1QTNF1 is expressed in the myocardium; however, its function in myocytes has not yet been investigated. OBJECTIVE: To systematically investigate the roles of C1QTNF1 in angiotensin II (Ang II)-induced cardiac hypertrophy. METHODS AND RESULTS: C1QTNF1 knock-out mice were used with the aim of determining the role of C1QTNF1 in cardiac hypertrophy in the adult heart...
June 2018: Free Radical Biology & Medicine
Feihong Yang, Li Xue, Ziqi Han, Feng Xu, Shengchuan Cao, Shuai Dai, Baoshan Liu, Qiuhuan Yuan, Zheng Wang, Ping Guo, Yuguo Chen
Visceral adipose tissue-derived serine protease inhibitor (vaspin), as a secretory adipokine, was reported to exert a protective role on insulin resistance. Recent studies showed that serum vaspin level was downregulated in patients with coronary artery disease. However, whether vaspin exerted specific effects on myocardial injury remains unknown. In this study, we determined to explore the role of vaspin overexpression in myocardial ischaemia/reperfusion (I/R) injury and the underlying mechanisms. Our results showed that the systemic delivery of adeno-associated virus-vaspin to mice reduced myocardial infarct size and apoptosis, and improved cardiac function after reperfusion, accompanied with upregulated autophagic flux and restored lysosomal function in the ischaemic heart...
June 30, 2018: Biochemical and Biophysical Research Communications
Jun Hou, Dezhi Zheng, Wenjing Xiao, Dandan Li, Jie Ma, Yonghe Hu
Mangiferin functions as a perfect anti-oxidative compound in the diabetic heart, however, the exact mechanism remains to be elucidated. Here, we show the cardioprotective effect of mangiferin under high glucose-induced cardiotoxic condition mainly contributed to enhanced autophagy via suppressing mTORC1 downstream signal transduction. Primary neonatal rat cardiomyocytes were cultured to detect myocytes injury, autophagy, and related signal transduction under different doses of glucose and mangiferin treatment...
2018: Frontiers in Pharmacology
Min Feng, Zongqing Li, Dong Wang, Fang Wang, Chenyan Wang, Chunfang Wang, Faming Ding
BACKGROUND: Myocardial infarction (MI), a leading cause of mortality, is identified as the myocardial necrosis due to prolonged ischemia. Hypoxia, resulting from ischemia, induces cell apoptosis during MI. Since miR-210 is a hypoxia inducible factor, we aimed to explore the functional role of miR-210 in hypoxic H9c2 cells. METHODS: Hypoxia-induced cell injury was evaluated according to cell viability, apoptosis and expression of apoptosis-associated proteins. miR-210 expression after hypoxia was tested...
June 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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