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cardiomyocyte and metabolism

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https://www.readbyqxmd.com/read/28445457/the-mitochondrial-na-ca-2-exchanger-is-essential-for-ca-2-homeostasis-and-viability
#1
Timothy S Luongo, Jonathan P Lambert, Polina Gross, Mary Nwokedi, Alyssa A Lombardi, Santhanam Shanmughapriya, April C Carpenter, Devin Kolmetzky, Erhe Gao, Jop H van Berlo, Emily J Tsai, Jeffery D Molkentin, Xiongwen Chen, Muniswamy Madesh, Steven R Houser, John W Elrod
Mitochondrial calcium (mCa(2+)) has a central role in both metabolic regulation and cell death signalling, however its role in homeostatic function and disease is controversial. Slc8b1 encodes the mitochondrial Na(+)/Ca(2+) exchanger (NCLX), which is proposed to be the primary mechanism for mCa(2+) extrusion in excitable cells. Here we show that tamoxifen-induced deletion of Slc8b1 in adult mouse hearts causes sudden death, with less than 13% of affected mice surviving after 14 days. Lethality correlated with severe myocardial dysfunction and fulminant heart failure...
April 26, 2017: Nature
https://www.readbyqxmd.com/read/28439717/negligible-effect-of-enos-palmitoylation-on-fatty-acid-regulation-of-contraction-in-ventricular-myocytes-from-healthy-and-hypertensive-rats
#2
Chun Li Jin, Yu Na Wu, Ji Hyun Jang, Zai Hao Zhao, Goo Taeg Oh, Sung Joon Kim, Yin Hua Zhang
S-palmitoylation is an important post-translational modification that affects the translocation and the activity of target proteins in a variety of cell types including cardiomyocytes. Since endothelial nitric oxide synthase (eNOS) is known to be palmitoylated and the activity of eNOS is essential in fatty acid-dependent β-oxidation in muscle, we aimed to test whether palmitoylation of eNOS is involved in palmitic acid (PA) regulation of left ventricular (LV) myocyte contraction from healthy (sham) and hypertensive (HTN) rats...
April 25, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28439258/diabetic-cardiomyopathy-an-immunometabolic-perspective
#3
REVIEW
Paras K Mishra, Wei Ying, Shyam Sundar Nandi, Gautam K Bandyopadhyay, Kaushik K Patel, Sushil K Mahata
The heart possesses a remarkable inherent capability to adapt itself to a wide array of genetic and extrinsic factors to maintain contractile function. Failure to sustain its compensatory responses results in cardiac dysfunction, leading to cardiomyopathy. Diabetic cardiomyopathy (DCM) is characterized by left ventricular hypertrophy and reduced diastolic function, with or without concurrent systolic dysfunction in the absence of hypertension and coronary artery disease. Changes in substrate metabolism, oxidative stress, endoplasmic reticulum stress, formation of extracellular matrix proteins, and advanced glycation end products constitute the early stage in DCM...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28437279/npy-impairs-cell-viability-and-mitochondrial-membrane-potential-through-ca2-and-p38-signaling-pathways-in-neonatal-rat-cardiomyocytes
#4
Jun Hu, Xuehua Xu, Yuanyi Zuo, Xiangting Gao, Yun Wang, Cunquan Xiong, Hongcheng Zhou, Shaohua Zhu
NPY is involved in stress cardiomyopathy (SCM). However, the associated mechanism for NPY-induced SCM remains unclear. In this study, we aimed to explore potential cell signaling pathways that are related to NPY-mediated cell viability in neonatal rat cardiomyocytes. We found that NPY induced cell viability suppression in cultured cardiomyocytes in a dose-dependent manner. After NPY treatment, the expression of CaN and p-CAMKII was increased significantly, and the phosphorylation of p38 but not ERK and JNK was detected...
April 18, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28432557/proteomic-analysis-of-mitochondrial-proteins-in-the-guinea-pig-heart-following-long-term-normobaric-hyperoxia
#5
Lucia Lichardusova, Zuzana Tatarkova, Andrea Calkovska, Daniela Mokra, Ivan Engler, Peter Racay, Jan Lehotsky, Peter Kaplan
Normobaric hyperoxia is applied for the treatment of a wide variety of diseases and clinical conditions related to ischemia or hypoxia, but it can increase the risk of tissue damage and its efficiency is controversial. In the present study, we analyzed cardiac mitochondrial proteome derived from guinea pigs after 60 h exposure to 100% molecular oxygen (NBO) or O2 enriched with oxygen cation (NBO+). Two-dimensional gel electrophoresis followed by MALDI-TOF/TOF mass spectrometry identified twenty-two different proteins (among them ten nonmitochondrial) that were overexpressed in NBO and/or NBO+ group...
April 21, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28430962/ulk1-prevents-cardiac-dysfunction-in-obesity-through-autophagy-meditated-regulation-of-lipid-metabolism
#6
Minae An, Dong-Ryeol Ryu, Jang Won Park, Ji Ha Choi, Eun-Mi Park, Kyung Eun Lee, Minna Woo, Minsuk Kim
Aims: Autophagy is essential to maintain tissue homeostasis, particularly in long-lived cells such as cardiomyocytes. Whereas many studies support the importance of autophagy in the mechanisms underlying obesity-related cardiac dysfunction, the role of autophagy in cardiac lipid metabolism remains unclear. In the heart, lipotoxicity is exacerbated by cardiac lipoprotein lipase (LPL), which mediates accumulation of fatty acids to the heart through intravascular triglyceride (TG) hydrolysis...
April 17, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28425109/alcoholic-cardiomyopathy-disrupted-protein-balance-and-impaired-cardiomyocyte-contractility
#7
Jennifer L Steiner, Charles H Lang
Alcoholic cardiomyopathy (ACM) can develop after consumption of relatively large amounts of alcohol over time or from acute binge drinking. Of the many factors implicated in the etiology of ACM, chronic perturbation in protein balance has been strongly implicated. This review focuses on recent contributions (since 2010) in the area of protein metabolism and cardiac function related to ACM. Data reviewed include that from in vitro and preclinical in vivo animal studies where alcohol or an oxidative metabolite was studied and outcome measures in either cardiomyocytes or whole heart pertaining to protein synthesis or degradation were reported...
April 20, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28421296/metabolite-signatures-of-doxorubicin-induced-toxicity-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#8
Umesh Chaudhari, James K Ellis, Vilas Wagh, Harshal Nemade, Jürgen Hescheler, Hector C Keun, Agapios Sachinidis
Drug-induced off-target cardiotoxicity, particularly following anti-cancer therapy, is a major concern in new drug discovery and development. To ensure patient safety and efficient pharmaceutical drug development, there is an urgent need to develop more predictive cell model systems and distinct toxicity signatures. In this study, we applied our previously proposed repeated exposure toxicity methodology and performed (1)H NMR spectroscopy-based extracellular metabolic profiling in culture medium of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) exposed to doxorubicin (DOX), an anti-cancer agent...
April 18, 2017: Amino Acids
https://www.readbyqxmd.com/read/28413577/circadian-control-of-cardiac-metabolism-physiologic-roles-and-pathologic-implications
#9
Martin E Young
Over the course of the day, the heart is challenged with dramatic fluctuations in energetic demand and nutrient availability. It is therefore not surprising that rhythms in cardiac metabolism have been reported at multiple levels, including the utilization of glucose, fatty acids, and amino acids. Evidence has emerged suggesting that the cardiomyocyte circadian clock is in large part responsible for governing cardiac metabolic rhythms. In doing so, the cardiomyocyte clock temporally partitions ATP generation for increased contractile function during the active period, promotes nutrient storage at the end of the active period, and facilitates protein turnover (synthesis and degradation) during the beginning of the sleep phase...
January 2017: Methodist DeBakey Cardiovascular Journal
https://www.readbyqxmd.com/read/28397099/maturation-of-human-pluripotent-stem-cell-derived-cardiomyocytes-is-improved-in-cardiovascular-construct
#10
Hanna Vuorenpää, Kirsi Penttinen, Tuula Heinonen, Mari Pekkanen-Mattila, Jertta-Riina Sarkanen, Timo Ylikomi, Katriina Aalto-Setälä
In order to translate preclinical data into the clinical studies, relevant in vitro models with structure and key functional properties similar to native human tissue should be used. In vitro cardiac models with vascular structures mimic the highly vascularized myocardium and provide interactions between endothelial cells, stromal cells and cardiomyocytes. Currently, human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have been shown to present immature morphology and fetal-like electrophysiological properties that may limit their use as physiological test platform...
April 10, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28396530/downregulation-of-plzf-gene-ameliorates-metabolic-and-cardiac-traits-in-the-spontaneously-hypertensive-rat
#11
František Liška, Vladimír Landa, Václav Zídek, Petr Mlejnek, Jan Šilhavý, Miroslava Šimáková, Hynek Strnad, Jaroslava Trnovská, Vojtěch Škop, Ludmila Kazdová, Colby G Starker, Daniel F Voytas, Zsuzsanna Izsvák, Massimiliano Mancini, Ondřej Šeda, Vladimír Křen, Michal Pravenec
The spontaneously hypertensive rat (SHR), one of the most widely used model of essential hypertension, is predisposed to left ventricular hypertrophy, myocardial fibrosis, and metabolic disturbances. Recently, quantitative trait loci influencing blood pressure, left ventricular mass, and heart interstitial fibrosis were genetically isolated within a minimal congenic subline that contains only 7 genes, including mutant Plzf (promyelocytic leukemia zinc finger) candidate gene. To identify Plzf as a quantitative trait gene, we targeted Plzf in the SHR using the transcription activator-like effector nuclease technique and obtained SHR line harboring targeted Plzf gene with a premature stop codon...
April 10, 2017: Hypertension
https://www.readbyqxmd.com/read/28395010/inflammation-and-metabolic-cardiomyopathy
#12
Kazuhiko Nishida, Kinya Otsu
Excessive feeding is associated with an increase in the incidence of chronic metabolic diseases, such as obesity, insulin resistance, and type 2 diabetes. Metabolic disturbance induces chronic low-grade inflammation in metabolically-important organs, such as the liver and adipose tissue. Many of the inflammatory signalling pathways are directly triggered by nutrients. The pro-inflammatory mediators in adipocytes and macrophages infiltrating adipose tissue promote both local and systemic pro-inflammatory status...
March 15, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28387734/cytotoxicity-of-zno-nanowire-arrays-on-excitable-cells
#13
Yongchen Wang, Yu Wu, Farhan Quadri, Jordan D Prox, Liang Guo
Zinc oxide (ZnO) nanowires have been widely studied for their applications in electronics, optics, and catalysts. Their semiconducting, piezoelectric, fluorescent, and antibacterial properties have also attracted broad interest in their biomedical applications. Thus, it is imperative to evaluate the biosafety of ZnO nanowires and their biological effects. In this study, the cellular level biological effects of ZnO nanowire arrays are specifically tested on three types of excitable cells, including NG108-15 neuronal cell line, HL-1 cardiac muscle cell line, and neonatal rat cardiomyocytes...
April 7, 2017: Nanomaterials
https://www.readbyqxmd.com/read/28384228/doxycycline-protects-against-ros-induced-mitochondrial-fragmentation-and-iso-induced-heart-failure
#14
Adam Riba, Laszlo Deres, Krisztian Eros, Aliz Szabo, Klara Magyar, Balazs Sumegi, Kalman Toth, Robert Halmosi, Eszter Szabados
In addition to their anti-bacterial action, tetracyclines also have complex biological effects, including the modification of mitochondrial protein synthesis, metabolism and gene-expression. Long-term clinical studies have been performed using tetracyclines, without significant side effects. Previous studies demonstrated that doxycycline (DOX), a major tetracyclin antibiotic, exerted a protective effect in animal models of heart failure; however, its exact molecular mechanism is still unknown. Here, we provide the first evidence that DOX reduces oxidative stress-induced mitochondrial fragmentation and depolarization in H9c2 cardiomyocytes and beneficially alters the expression of Mfn-2, OPA-1 and Drp-1 -the main regulators of mitochondrial fusion and fission-in our isoproterenol (ISO)-induced heart failure model, ultimately decreasing the severity of heart failure...
2017: PloS One
https://www.readbyqxmd.com/read/28376365/bioacoustic-enabled-patterning-of-human-ipsc-derived-cardiomyocytes-into-3d-cardiac-tissue
#15
Vahid Serpooshan, Pu Chen, Haodi Wu, Soah Lee, Arun Sharma, Daniel A Hu, Sneha Venkatraman, Adarsh Venkataraman Ganesan, Osman Berk Usta, Martin Yarmush, Fan Yang, Joseph C Wu, Utkan Demirci, Sean M Wu
The creation of physiologically-relevant human cardiac tissue with defined cell structure and function is essential for a wide variety of therapeutic, diagnostic, and drug screening applications. Here we report a new scalable method using Faraday waves to enable rapid aggregation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) into predefined 3D constructs. At packing densities that approximate native myocardium (10(8)-10(9) cells/ml), these hiPSC-CM-derived 3D tissues demonstrate significantly improved cell viability, metabolic activity, and intercellular connection when compared to constructs with random cell distribution...
July 2017: Biomaterials
https://www.readbyqxmd.com/read/28374891/short-term-hypoxia-reverses-ox-ldl-induced-cd36-and-glut4-switching-metabolic-pathways-in-h9c2-cardiomyoblast-cells
#16
Yeh-Peng Chen, Hsi-Hsien Hsu, Rathinasamy Baskaran, Su-Ying Wen, Chia-Yao Shen, Cecilia-Hsuan Day, Tsung-Jung Ho, Viswanadha Vijaya Padma, Wei-Wen Kuo, Chih-Yang Huang
High levels of circulating low-density lipoproteins (LDL, plasma proteins that carry cholesterol and triglycerides) are associated with type 2 diabetes, arteriosclerosis, obesity and hyperlipidemia. In the heart, the accumulation of oxidized low-density lipoprotein (Ox-LDL) has been proposed to play a role in the development of cardiovascular disease. We obtain cholesterol from animals and animal-derived foods such as milk, eggs and cheese. In previous studies, the ratio of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) was shown to be important for our health...
April 4, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28361977/myocardial-stress-and-autophagy-mechanisms-and-potential-therapies
#17
REVIEW
Lea M D Delbridge, Kimberley M Mellor, David J Taylor, Roberta A Gottlieb
Autophagy is a ubiquitous cellular catabolic process responsive to energy stress. Research over the past decade has revealed that cardiomyocyte autophagy is a prominent homeostatic pathway, important in adaptation to altered myocardial metabolic demand. The cellular machinery of autophagy involves targeted direction of macromolecules and organelles for lysosomal degradation. Activation of autophagy has been identified as cardioprotective in some settings (that is, ischaemia and ischaemic preconditioning). In other situations, sustained autophagy has been linked with cardiopathology (for example, sustained pressure overload and heart failure)...
March 31, 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/28357065/role-of-micrornas-in-the-pathogenesis-of-diabetic-cardiomyopathy
#18
Xinyu Liu, Shixue Liu
The morbidity of diabetes mellitus has been increasing annually. As a progressive metabolic disorder, chronic complications occur in the late stage of diabetes. In addition, cardiovascular diseases account for the major cause of morbidity and mortality among the diabetic population worldwide. Diabetic cardiomyopathy (DCM) is a type of diabetic heart disease. Patients with DCM show symptoms and signs of heart failure while no specific cause, such as coronary disease, hypertension, alcohol consumption, or other structural heart diseases has been identified...
February 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28352650/point-mutations-in-murine-nkx2-5-phenocopy-human-congenital-heart-disease-and-induce-pathogenic-wnt-signaling
#19
Milena B Furtado, Julia C Wilmanns, Anjana Chandran, Joelle Perera, Olivia Hon, Christine Biben, Taylor J Willow, Hieu T Nim, Gurpreet Kaur, Stephanie Simonds, Qizhu Wu, David Willians, Ekaterina Salimova, Nicolas Plachta, James M Denegre, Stephen A Murray, Diane Fatkin, Michael Cowley, James T Pearson, David Kaye, Mirana Ramialison, Richard P Harvey, Nadia A Rosenthal, Mauro W Costa
Mutations in the Nkx2-5 gene are a main cause of congenital heart disease. Several studies have addressed the phenotypic consequences of disrupting the Nkx2-5 gene locus, although animal models to date failed to recapitulate the full spectrum of the human disease. Here, we describe a new Nkx2-5 point mutation murine model, akin to its human counterpart disease-generating mutation. Our model fully reproduces the morphological and physiological clinical presentations of the disease and reveals an understudied aspect of Nkx2-5-driven pathology, a primary right ventricular dysfunction...
March 23, 2017: JCI Insight
https://www.readbyqxmd.com/read/28350193/reconstitution-of-hur-inhibited-cugbp1-expression-protects-cardiomyocytes-from-acute-myocardial-infarction-induced-injury
#20
Lei Gu, Huiwen Wang, Jun Wang, Yuting Guo, Yinglong Tang, Yang Mao, Lijuan Chen, Hua Lou, Guangju Ji
AIM: Myocardial infarction (MI) is one of the leading causes of death in elderly people. Expanding the knowledge of the molecular mechanisms underlying MI is of profound importance to developing a cure for MI. The CUGBP- and ETR-3-like factor (CELF) proteins, a family of RNA-binding proteins, play key roles in RNA metabolism. To determine the functions and molecular mechanisms of CELF proteins in MI, an animal model of acute myocardial infarction (AMI) was used in our study. RESULTS: We found that the CUG triplet repeat RNA-binding protein 1 (CUGBP1)/CELF1 expression levels were decreased in AMI-injured hearts, and further studies showed that two highly conserved adenylate-uridylate-rich (AU-rich) elements in the 3'UTR of CUGBP1 were responsible for the decreased CUGBP1 expression...
March 28, 2017: Antioxidants & Redox Signaling
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