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Cardiomyocytes and mToR

Yafan Gong, Jie Yang, Jingzeng Cai, Qi Liu, Jun Min Zhang, Ziwei Zhang
Glutathione peroxidase 3 (Gpx3), as an important selenoprotein, is the most crucial antioxidant defense in cardiomyocytes. However, the role of Gpx3 in Se-deficient cardiomyocyte damage still less reported. Here, we developed Gpx3 silence cardiomyocytes culture model (small interfering RNA; siRNA) for research the crosstalk between autophagy and apoptosis. Quantitative real-time PCR and western blot analysis are performed to detect the expression of apoptosis and autophagy-related genes. MDC stain, flow cytometry, AO/EB stain, and electron microscope were performed to observe the changes of cell morphology...
December 4, 2018: Journal of Cellular Physiology
Aiping Wu, Pengfei Hu, Jian Lin, Wan Xia, Rui Zhang
Cannabinoid receptor 2 (CB2 ) has been reported to produce a cardio-protective effect in cardiovascular diseases such as myocardial infarction. Here in this study, we investigated the role of CB2 in diabetic cardiomyopathy (DCM) and its underlying mechanisms. HU308 was used for the selective activation of CB2 . Bafilomycin A1 was used for the blockade of autophagy and compound C was used to inhibit AMPK signaling. An streptozotocin (STZ)-induced mice model and high glucose (HG)-challenged cardiomyocytes were applied for study...
2018: Frontiers in Pharmacology
Liuhui Chang, Xiaoming Chai, Peiming Chen, Jianfang Cao, Hong Xie, Jiang Zhu
This study aimed to investigate the role of microRNA‑181b‑5p (miR‑181b‑5p) in starvation‑induced cardiomyocyte autophagy by targeting heat shock protein family A member 5 (Hspa5). For this purpose, H9c2 cardiomyocytes and neonatal rat ventricular myocytes (NRVMs) were glucose‑starved in Earle's Balanced Salt Solution (EBSS) for different periods of time (0, 2, 4, 6 and 8 h). RT‑qPCR analysis was performed to examine the expression of miR‑181b‑5p in the different groups. Immunofluorescence was performed to detect the expression of LC3...
January 2019: International Journal of Molecular Medicine
Chen Chen, Lei-Xin Zou, Qiu-Yue Lin, Xiao Yan, Hai-Lian Bi, Xin Xie, Shuai Wang, Qing-Shan Wang, Yun-Long Zhang, Hui-Hua Li
Sustained cardiac hypertrophy is a major cause of heart failure (HF) and death. Recent studies have demonstrated that resveratrol (RES) exerts a protective role in hypertrophic diseases. However, the molecular mechanisms involved are not fully elucidated. In this study, cardiac hypertrophic remodeling in mice were established by pressure overload induced by transverse aortic constriction (TAC). Cardiac function was evaluated by echocardiography and invasive pressure-volume analysis. Cardiomyocyte size was detected by wheat germ agglutinin staining...
November 1, 2018: Redox Biology
Guangyao Huang, Liang Yang, Wei Zhou, Xianglin Tang, Yuguang Wang, Zengchun Ma, Shan Gao, Yue Gao
To investigate the toxicity of water and ethanol "Fuzi" (FZ) extracts and to explore the toxicity mechanism in rats. Water and ethanol extracts were prepared. Three groups of rats received the water extract, ethanol extract, or water by oral gavage for seven days. Pathological section staining of heart tissue. Colorimetric analysis was used to determine serum lactate dehydrogenase. The metabolic expression of small molecules in rats was measured by a metabolomics method. Western blotting was used to detect the expression of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR), transforming growth factor-β1 (TGF-β1), and caspase-3...
November 7, 2018: International Journal of Molecular Sciences
Maiko Ohashi, Kazumasa Okubo, Sakiko Mizuno, Masaki Yoda, Hideyuki Shirasawa, Kazuhiro Chiba, Keisuke Horiuchi, Morio Matsumoto, Masaya Nakamura
Granulocyte-colony stimulating factor (G-CSF) is a cytokine crucially involved in the regulation of granulopoiesis and the mobilization of hematopoietic stem cells from bone marrow. However, emerging data suggest that G-CSF exhibits more diverse functions than initially expected, such as conferring protection against apoptosis to neural cells and stimulating mitogenesis in cardiomyocytes and skeletal muscle stem cells after injury. In the present study, we sought to investigate the potential contribution of G-CSF to the regulation of muscle volume...
November 3, 2018: Biochemical and Biophysical Research Communications
Mengqiu Dang, Xiangjun Zeng, Buxing Chen, Hongxia Wang, Huihua Li, Yu Liu, Xiuling Zhang, Xianxian Cao, Fenghe Du, Caixia Guo
The pathogenesis of myocardial ischemia/reperfusion (I/R) is poorly understood, but recent evidence suggests that autophagy plays crucial roles in I/R injuries. Soluble receptor for advanced glycation end-products (sRAGE) exerts protective effects during I/R by decreasing cardiac apoptosis, which is mediated via increasing the ubiquitin proteasome system (UPS) and signal transducer and activator of transcription 3 (STAT3). The present study examined the effects and mechanisms of sRAGE on I/R-triggered cardiac autophagy...
October 25, 2018: Free Radical Biology & Medicine
Bin Dong, Chen Liu, Ruicong Xue, Yan Wang, Yu Sun, Zhuomin Liang, Wendong Fan, Jingzhou Jiang, Jingjing Zhao, Qiao Su, Gang Dai, Yugang Dong, Huiling Huang
Cardiac hypertrophy is a pathophysiological response to various pathological stresses and ultimately leads to heart failure. Oxidative stress is one of the critical processes involved in hypertrophy development. Fisetin, a small molecular flavonoid, has been shown to have anti-oxidative, anti-proliferative and anti-inflammatory properties. However, the effect of fisetin on cardiac hypertrophy remains unknown. In our present study, we showed that fisetin inhibited pressure overload-induced cardiac hypertrophy, improved cardiac function in vivo and suppressed phenylephrine (PE)-induced cardiomyocyte hypertrophy in vitro...
December 2018: Journal of Nutritional Biochemistry
Jinjing Yang, Jiyao Xu, Xuebin Han, Hao Wang, Yuean Zhang, Jin Dong, Yongzhi Deng, Jingping Wang
Background: Lysophosphatidic acid (LPA), as a phospholipid signal molecule, participates in the regulation of various biological functions. Our previous study demonstrated that LPA induces cardiomyocyte hypertrophy in vitro ; however, the functional role of LPA in the post-infarct heart remains unknown. Growing evidence has demonstrated that autophagy is involved in regulation of cardiac hypertrophy. The aim of the current work was to investigate the effects of LPA on cardiac function and hypertrophy during myocardial infarction (MI) and determine the regulatory role of autophagy in LPA-induced cardiomyocyte hypertrophy...
2018: Frontiers in Physiology
Jinghai Hua, Zhanghua Liu, Zuheng Liu, Dongqi An, Wenyan Lai, Qiong Zhan, Qingchun Zeng, Hao Ren, Dingli Xu
BACKGROUND Cardiac rupture often occurs after acute myocardial infarction due to complex and unclear pathogenesis. This study investigated whether metformin increases the incidence of cardiac rupture after myocardial infarction through the AMPK-MTOR/PGC-1α signaling pathway. MATERIAL AND METHODS An acute myocardial infarction (MI) mouse model was established. A series of experiments involving RT-qPCR, Western blot, TUNEL staining, and Masson staining were performed in this study. RESULTS Myocardial infarction occurred, resulting in the cardiac rupture, and the expression level of PGC-1α increased in the cardiac myocardium...
October 2, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Han-Hua Zhu, Xian-Tao Wang, Yu-Han Sun, Wen-Kai He, Jia-Bao Liang, Bing-Hai Mo, Lang Li
BACKGROUND/AIMS: Microvascular obstruction (MVO), an undesirable complication of percutaneous coronary intervention, is independently associated with adverse left ventricle remodeling and poor prognosis after acute myocardial infarction. Hypoxia and oxidative stress major roles in the pathophysiology of MVO. Pim1 serves an important protective role in the ischemic myocardium, but the underlying mechanisms remain poorly defined. Autophagy in early hypoxia or during moderate oxidative stress has been demonstrated to protect the myocardium...
2018: Cellular Physiology and Biochemistry
Wei You, Zhiming Wu, Fei Ye, Xiangqi Wu
The mTORC1-dependent signaling pathway is mainly involved in the adverse left ventricular remodeling (ALVR) process after myocardial infarction (MI). However, whether mTORC1 inhibition by cardamonin attenuates ALVR after MI is still not reported. Twenty mice were randomly assigned into three groups: sham group (10 ml/kg/day PBS, n=6), model group (MI and 10 ml/kg/day PBS, n=7) and cardamonin-treated group (MI and 20 mg/kg/day cardamonin, n=7). All groups received an intraperitoneal injection accordingly for two weeks...
September 1, 2018: Die Pharmazie
Hong Zhu, Wei Cao, Peng Zhao, Jieyu Wang, Yuying Qian, Yun Li
Hyperosmotic stress may be initiated during a diverse range pathological circumstances, which in turn results in tissue damage. In this process, the activation of survival signaling, which has the capacity to restore cell homeostasis, determines cell fate. Autophagy is responsible for cell survival and is activated by various pathological stimuli. However, its interplay with hyperosmotic stress and its effect on terminally differentiated cardiac myocytes is unknown. Nuclear factor of activated T‑cells 5 (NFAT5), an osmo‑sensitive transcription factor, mediates the expression of cell survival associated‑genes under hyperosmotic conditions...
September 12, 2018: International Journal of Molecular Medicine
Joseph C Godoy, Ingrid R Niesman, Anna R Busija, Adam Kassan, Jan M Schilling, Anna Schwarz, Erika A Alvarez, Nancy D Dalton, John C Drummond, David M Roth, Georgios Kararigas, Hemal H Patel, Alice E Zemljic-Harpf
Statins, which reduce LDL-cholesterol by inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, are among the most widely prescribed drugs. Skeletal myopathy is a known statin-induced adverse effect associated with mitochondrial changes. We hypothesized that similar effects would occur in cardiac myocytes in a lipophilicity-dependent manner between 2 common statins: atorvastatin (lipophilic) and pravastatin (hydrophilic). Neonatal cardiac ventricular myocytes were treated with atorvastatin and pravastatin for 48 h...
August 31, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Sukka Santosh Reddy, Heena Agarwal, Manoj Kumar Barthwal
Cilostazol (Ciloz) a potent Type III phosphodiesterase inhibitor is effective against inflammation, insulin resistance and cardiomyopathy. However, the effect of Ciloz on obesity-associated left ventricular diastolic dysfunction has not been explored yet. Hence, we examined the effect of Ciloz on cardiac remodelling and dysfunction in non-obese and obese-insulin resistant mice infused with AngiotensinII (AngII). Male C57BL/6 J mice were initially subjected to 19 weeks of chow or high fat diet (HFD) regimen and thereafter animals were randomised for AngII (1500 ng/kg/min, s...
October 2018: Journal of Molecular and Cellular Cardiology
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)...
August 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...
September 10, 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...
October 2018: Biochimica et biophysica acta. Molecular basis of disease
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
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