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cardiomyocyte and metabolism

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https://www.readbyqxmd.com/read/28807695/doxorubicin-enhance-oxysterol-levels-resulting-in-a-lxr-mediated-upregulation-of-cardiac-cholesterol-transporters
#1
Judith V Monzel, Thomas Budde, Henriette E Meyer Zu Schwabedissen, Matthias Schwebe, Sandra Bien-Möller, Dieter Lütjohann, Heyo K Kroemer, Gabriele Jedlitschky, Markus Grube
The anthracycline-mediated cardiotoxicity is still not completely understood. To examine the impact of cholesterol metabolism and transport in this context, cholesterol and oxysterol levels as well as the expression of the cholesterol transporters ABCA1 and ABCG1 were analyzed in doxorubicin-treated HL-1 murine cardiomyocytes as well as in mouse model for acute doxorubicin-induced cardiotoxicity. Doxorubicin-treated HL-1 cells exhibited enhanced cholesterol (153±20% of control), oxysterol (24S-hydroxycholesterol: 206±29% of control) and cholesterol precursor levels (lathosterol: 122±12% of control; desmosterol: 188±10% of control) indicating enhanced cholesterol synthesis...
August 11, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28795720/restoring-calcium-homeostasis-in-diabetic-cardiomyocytes-an-investigation-through-mathematical-modelling
#2
Phonindra Nath Das, Ajay Kumar, Nandadulal Bairagi, Samrat Chatterjee
Calcium homeostasis is a key factor in the regulation of cardiac excitation-contraction coupling. Calcium dynamics in cardiomyocytes is governed by ATP which depends on insulin dependent glucose concentration, via the glucose transporter type 4 (GLUT4) transporter. It would therefore be interesting to see how calcium dynamics changes in a cardiomyocyte under diabetic conditions. We proposed and analysed a four dimensional ordinary differential equation (ODE) model to capture the interdependency of calcium dynamics on glucose uptake and ATP generation...
August 10, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28781146/the-impact-of-foxo-1-to-cardiac-pathology-in-diabetes-mellitus-and-diabetes-related-metabolic-abnormalities
#3
Dimitry A Chistiakov, Alexander N Orekhov, Yuri V Bobryshev
Diabetic heart pathology has a serious social impact due to high prevalence worldwide and significant mortality/invalidation of diabetic patients suffered from cardiomyopathy. The pathogenesis of diabetic and diabetes-related cardiomyopathy is associated with progressive loss and impairment of cardiac function due to adverse effects of metabolic, prooxidant, proinflammatory, and pro-apoptotic stress factors. In the adult heart, the transcriptional factor forkhead box-1 (FOXO-1) is involved in maintaining cardiomyocytes in the homeostatic state and induction of their adaptation to metabolic and pro-oxidant stress stimuli...
August 2, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28771625/inhibition-of-dipeptidyl-peptidase-4-ameliorates-cardiac-ischemia-and-systolic-dysfunction-by-up-regulating-the-fgf-2-egr-1-pathway
#4
Masayoshi Suda, Ippei Shimizu, Yohko Yoshida, Yuka Hayashi, Ryutaro Ikegami, Goro Katsuumi, Takayuki Wakasugi, Yutaka Yoshida, Shujiro Okuda, Tomoyoshi Soga, Tohru Minamino
Dipeptidyl peptidase 4 inhibitors are used worldwide in the management of diabetes, but their role in the prevention or treatment of cardiovascular disorders has yet to be defined. We found that linagliptin, a DPP-4 inhibitor, suppressed capillary rarefaction in the hearts of mice with dietary obesity. Metabolomic analysis performed with capillary electrophoresis/mass spectrometry (LC-MS/MS) showed that linagliptin promoted favorable metabolic remodeling in cardiac tissue, which was characterized by high levels of citrulline and creatine...
2017: PloS One
https://www.readbyqxmd.com/read/28770953/microrna-200c-exacerbates-the-ischemia-reperfusion-injury-of-heart-through-targeting-the-glutaminase-gls-mediated-glutamine-metabolism
#5
F Liu, Y Li, G Liu
OBJECTIVE: Cardiac ischemia and reperfusion, the common pathophysiological processes during cardiovascular surgery, are followed by oxidative stresses during the restoration of blood flow to the tissue, known as ischemia/reperfusion (IR) injury. microRNAs (miRNAs) are a group of endogenous, short and noncoding RNAs that post-transcriptionally repress their target mRNA expressions. Currently, the roles of microRNAs in the IR are still under investigated. This study will investigate the roles and mechanisms of miRNAs in the ischemia/reperfusion injury of the heart...
July 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28760703/berberine-induced-cardioprotection-and-sirt3-modulation-in-doxorubicin-treated-h9c2-cardiomyoblasts
#6
Ana R Coelho, Tatiana R Martins, Renata Couto, Cláudia Deus, Cláudia V Pereira, Rui F Simões, Albert A Rizvanov, Filomena Silva, Teresa Cunha-Oliveira, Paulo J Oliveira, Teresa L Serafim
Doxorubicin (DOX) is one of the most widely used anti-neoplastic agents. However, treatment with DOX is associated with cumulative cardiotoxicity inducing progressive cardiomyocyte death. Sirtuin 3 (Sirt3), a mitochondrial deacetylase, regulates the activity of proteins involved in apoptosis, autophagy and metabolism. Our hypothesis is that pharmacological modulation by berberine (BER) pre-conditioning of Sirt3 protein levels decreases DOX-induced cardiotoxicity. Our results showed that DOX induces cell death in all experimental groups...
July 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28754449/the-role-of-nadph-oxidases-in-diabetic-cardiomyopathy
#7
REVIEW
Synne S Hansen, Ellen Aasum, Anne D Hafstad
Systemic changes during diabetes such as high glucose, dyslipidemia, hormonal changes and low grade inflammation, are believed to induce structural and functional changes in the cardiomyocyte associated with the development of diabetic cardiomyopathy. One of the hallmarks of the diabetic heart is increased oxidative stress. NADPH-oxidases (NOXs) are important ROS-producing enzymes in the cardiomyocyte mediating both adaptive and maladaptive changes in the heart. NOXs have been suggested as a therapeutic target for several diabetic complications, but their role in diabetic cardiomyopathy is far from elucidated...
July 25, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28742954/carbon-dioxide-elimination-by-cardiomyocytes-a-tale-of-high-carbonic-anhydrase-activity-and-membrane-permeability
#8
EDITORIAL
Erik R Swenson
Life as a multicellular organism requires a heart with a coordinated contractile activity that must never cease, and in this regard, it is very much like the brain with a high mass-specific 'resting' metabolic rate. To maintain this constant activity requires a high rate of oxygen consumption and resultant carbon dioxide generation and, pari passu, the rapid exchange of large amounts of these gases with capillary blood. While oxygen has been far more the focus of the two gases in cardiac physiology, the work of Arias-Hidalgo et al (1) in this issue of the journal offers new insights and better understanding of how CO2 uniquely traverses its path from production in the mitochondria to the capillary blood, and does so with much smaller driving gradients than necessary for oxygen...
July 25, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28740146/in-vivo-imaging-to-monitor-differentiation-and-therapeutic-effects-of-transplanted-mesenchymal-stem-cells-in-myocardial-infarction
#9
Zhijun Pei, Jing Zeng, Yafeng Song, Yan Gao, Ruimin Wu, Yijia Chen, Fuyan Li, Wei Li, Hong Zhou, Yi Yang
Here, we used a noninvasive multimodality imaging approach to monitor differentiation of transplanted bone marrow mesenchymal stem cells (BMSCs) and recovery of cardiac function in an in vivo model of myocardial infarction (MI). We established a rat MI model by coronary artery ligation. Ninety rats were randomly assigned into four groups: sham-operated, MI model, and α-MHC-HSV1-tk-transfected or un-transfected BMSCs-treated MI model. We used (18)F-Fluro-deoxyglucose ((18)F-FDG) positron emission tomography (PET) to monitor recovery of cardiac function, and (18)F-FHBG PET/CT imaging to monitor transplanted BMSCs differentiation 24 h after (18)F-FDG imaging...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28737513/loss-of-function-mutations-in-co-chaperone-bag3-destabilize-small-hsps-and-cause-cardiomyopathy
#10
Xi Fang, Julius Bogomolovas, Tongbin Wu, Wei Zhang, Canzhao Liu, Jennifer Veevers, Matthew J Stroud, Zhiyuan Zhang, Xiaolong Ma, Yongxin Mu, Dieu-Hung Lao, Nancy D Dalton, Yusu Gu, Celine Wang, Michael Wang, Yan Liang, Stephan Lange, Kunfu Ouyang, Kirk L Peterson, Sylvia M Evans, Ju Chen
Defective protein quality control (PQC) systems are implicated in multiple diseases. Molecular chaperones and co-chaperones play a central role in functioning PQC. Constant mechanical and metabolic stress in cardiomyocytes places great demand on the PQC system. Mutation and downregulation of the co-chaperone protein BCL-2-associated athanogene 3 (BAG3) are associated with cardiac myopathy and heart failure, and a BAG3 E455K mutation leads to dilated cardiomyopathy (DCM). However, the role of BAG3 in the heart and the mechanisms by which the E455K mutation leads to DCM remain obscure...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28736261/genetic-disruption-of-the-cardiomyocyte-circadian-clock-differentially-influences-insulin-mediated-processes-in-the-heart
#11
Graham R McGinnis, Yawen Tang, Rachel A Brewer, Manoja K Brahma, Haley L Stanley, Gobinath Shanmugam, Namakkal Soorappan Rajasekaran, Glenn C Rowe, Stuart J Frank, Adam R Wende, E Dale Abel, Heinrich Taegtmeyer, Silvio Litovsky, Victor Darley-Usmar, Jianhua Zhang, John C Chatham, Martin E Young
Cardiovascular physiology exhibits time-of-day-dependent oscillations, which are mediated by both extrinsic (e.g., environment/behavior) and intrinsic (e.g., circadian clock) factors. Disruption of circadian rhythms negatively affects multiple cardiometabolic parameters. Recent studies suggest that the cardiomyocyte circadian clock directly modulates responsiveness of the heart to metabolic stimuli (e.g., fatty acids) and stresses (e.g., ischemia/reperfusion). The aim of this study was to determine whether genetic disruption of the cardiomyocyte circadian clock impacts insulin-regulated pathways in the heart...
July 20, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28736181/succinate-accumulation-impairs-cardiac-pyruvate-dehydrogenase-activity-through-grp91-dependent-and-independent-signaling-pathways-therapeutic-effects-of-ginsenoside-rb1
#12
Jia Li, Yi-Lin Yang, Lan-Zhu Li, Lei Zhang, Qun Liu, Kang Liu, Ping Li, Baolin Liu, Lian-Wen Qi
Altered mitochondrial oxidation increases vulnerability to cardiac ischemia/reperfusion (I/R) injury in metabolic disorders. However, the metabolic signaling responsible for the dysfunction remains partly unknown. We sought to test whether or not hypoxic succinate accumulation could inhibit pyruvate dehydrogenase (PDH) activity and subsequently aggravate I/R injury. Results showed that saturated fatty acid palmitate stimulation increased fatty acid oxidation and induced hypoxia in cardiomyocytes, leading to succinate accumulation...
July 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28734787/selenium-deficiency-induced-thioredoxin-suppression-and-thioredoxin-knock-down-disbalanced-insulin-responsiveness-in-chicken-cardiomyocytes-through-pi3k-akt-pathway-inhibition
#13
Jie Yang, Sattar Hamid, Jingzeng Cai, Qi Liu, Shiwen Xu, Ziwei Zhang
Thioredoxin (Txn) system is the most crucial antioxidant defense mechanism in cell consisting of Txn, thioredoxin reductase (TR) and Nicotinamide Adenine Dinucleotide Phosphate (NADPH). Perturbations in Txn system may compromise cell survival through oxidative stress induction. Metabolic activity of insulin plays important roles in fulfilling the stable and persistent demands of heart through glucose metabolism. However, the roles of Txn and Txn system in insulin modulated cardiac energy metabolism have been less reported...
July 19, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28729453/pi3k-and-calcium-signaling-in-cardiovascular-disease
#14
REVIEW
Alessandra Ghigo, Muriel Laffargue, Mingchuan Li, Emilio Hirsch
Receptor signaling relays on intracellular events amplified by secondary and tertiary messenger molecules. In cardiomyocytes and smooth muscle cells, cyclic AMP (cAMP) and subsequent calcium (Ca(2+)) fluxes are the best characterized receptor-regulated signaling events. However, most of receptors able to modify contractility and other intracellular responses signal through a variety of other messengers, and whether these signaling events are interconnected has long remained unclear. For example, the PI3K (phosphoinositide 3-kinase) pathway connected to the production of the lipid second messenger PIP3/PtdIns(3,4,5)P3 (phosphatidylinositol (3,4,5)-trisphosphate) is potentially involved in metabolic regulation, activation of hypertrophy, and survival pathways...
July 21, 2017: Circulation Research
https://www.readbyqxmd.com/read/28723590/cardioprotective-mitochondrial-binding-by-hexokinase-i-is-induced-by-a-hyperoxic-acute-thermal-insult-in-the-rainbow-trout-oncorhynchus-mykiss
#15
Neal Ingraham Callaghan, Kenneth Javier Williams, Tyson James MacCormack
Due to the substantial photosynthetic biomass in their habitat, salmonids such as the rainbow trout (Oncorhynchus mykiss) can be subject to hyperoxia in addition to high temperatures associated with climate change. Both stressful conditions increase the incidence of damaging reactive oxygen species (ROS). The mitochondrial association of hexokinase has been shown to increase in the hearts of certain fish experiencing hypoxia in a putative cardioprotective response to oxidative stress. In this study, the mitochondrial association of hexokinase I (HKI) and markers of oxidative damage and metabolic stress were probed to elucidate the cardioprotective role of hexokinase in the rainbow trout...
July 16, 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/28721709/-paradoxal-decrease-and-metabolic-effects-of-bnp-in-obese-patient
#16
Rémy C Martin-Du-Pan, Alain Golay
Natriuretic peptides (NP), ANP and BNP, are produced by cardiomyocytes when there is stretching of the ventricular and auricular walls in heart failure (HF). Their vasodilatator and natriuretic effect oppose to volume and pressure overload occurring in HF. Several studies have observed decreased levels of NP in obese and diabetic people and in patients with insulin resistance. This decrease could contribute to hypertension, frequently observed in obesity. NP have also a lipolytic action. Low levels of NP could promote obesity...
March 22, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28716730/interaction-of-small-g-protein-signaling-modulator-3-with-connexin-43-contributes-to-myocardial-infarction-in-rat-hearts
#17
Chang Youn Lee, Jung-Won Choi, Sunhye Shin, Jiyun Lee, Hyang-Hee Seo, Soyeon Lim, Seahyoung Lee, Hyun-Chul Joo, Sang Woo Kim, Ki-Chul Hwang
Connexin 43 (Cx43), a ubiquitous connexin expressed in the heart and skin, is associated with a variety of hereditary conditions. Therefore, the characterization of Cx43-interacting proteins and their dynamics is important to understand not only the molecular mechanisms underlying pathological malfunction of gap junction-mediated intercellular communication but also to identify novel and unanticipated biological functions of Cx43. In the present study, we observed potential targets of Cx43 to determine new molecular functions in cardio-protection...
July 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28709867/attenuation-of-the-hypoxia-induced-mir-34a-protects-cardiomyocytes-through-maintenance-of-glucose-metabolism
#18
Zai-Cun Wang, Zun-Zhe Wang, Huan-Ju Ma, Chen-Chen Wang, Hua-Ting Wang
Ischemic injury in the heart is associated with death of cardiomyocytes and even after decades of research there is no appropriate therapeutic intervention to treat ischemic injury. The microRNA miR-34a is known to be induced in cardiomyocytes following ischemic injury. Another hallmark of ischemic injury is impaired glycolysis. The objective of the current study was to investigate the effects of short- and long-term exposure to hypoxia on miR-34a expression on apoptosis and regulation of key glycolysis metabolic enzymes...
July 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28706006/integration-of-flux-measurements-to-resolve-changes-in-anabolic-and-catabolic-metabolism-in-cardiac-myocytes
#19
Andrew A Gibb, Pawel K Lorkiewicz, Yu-Ting Zheng, Xiang Zhang, Aruni Bhatnagar, Steven P Jones, Bradford G Hill
Although ancillary pathways of glucose metabolism are critical for synthesizing cellular building blocks and modulating stress responses, how they are regulated remains unclear. In the present study, we used radiometric glycolysis assays, [(13)C6]-glucose isotope tracing, and extracellular flux analysis to understand how phosphofructokinase (PFK)-mediated changes in glycolysis regulate glucose carbon partitioning into catabolic and anabolic pathways. Expression of kinase-deficient or phosphatase-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in rat neonatal cardiomyocytes co-ordinately regulated glycolytic rate and lactate production...
August 7, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28702068/hyperglycemia-induced-oxidative-stress-and-heart-disease-cardioprotective-effects-of-rooibos-flavonoids-and-phenylpyruvic-acid-2-o-%C3%AE-d-glucoside
#20
REVIEW
Phiwayinkosi V Dludla, Elizabeth Joubert, Christo J F Muller, Johan Louw, Rabia Johnson
Diabetic patients are at an increased risk of developing heart failure when compared to their non-diabetic counter parts. Accumulative evidence suggests chronic hyperglycemia to be central in the development of myocardial infarction in these patients. At present, there are limited therapies aimed at specifically protecting the diabetic heart at risk from hyperglycemia-induced injury. Oxidative stress, through over production of free radical species, has been hypothesized to alter mitochondrial function and abnormally augment the activity of the NADPH oxidase enzyme system resulting in accelerated myocardial injury within a diabetic state...
2017: Nutrition & Metabolism
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