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https://www.readbyqxmd.com/read/28439258/diabetic-cardiomyopathy-an-immunometabolic-perspective
#1
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/28436536/early-vertebrate-origin-and-diversification-of-small-transmembrane-regulators-of-cellular-ion-transport
#2
Sergej Pirkmajer, Henriette Kirchner, Leonidas Lundell, Pavel V Zelenin, Juleen R Zierath, Kira S Makarova, Yuri I Wolf, Alexander V Chibalin
Small transmembrane proteins are important for regulation of cellular ion transport. The most prominent among these proteins are members of the FXYD family (FXYD1-12), which regulate Na(+) -K(+) -ATPase, and phospholamban, sarcolipin, myoregulin, and DWORF, which regulate the sarco-endoplasmic reticulum Ca(2+) -ATPase (SERCA). FXYDs and regulators of SERCA are present in fishes, as well as terrestrial vertebrates; however, their evolutionary origins and phylogenetic relationships are obscure, thus hampering comparative physiological studies...
April 24, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28423119/importance-of-serca2a-on-early-isolated-diastolic-dysfunction-induced-by-supravalvular-aortic-stenosis-in-rats
#3
C F S M P Silveira, D H S Campos, P P Freire, A F Deus, K Okoshi, C R Padovani, A C Cicogna
Cardiac remodeling is defined as changes in shape and function of the heart in response to aggression (pressure overload). The sarcoplasmic reticulum calcium ATPase cardiac isoform 2a (SERCA2a) is a known factor that influences function. A wide spectrum of studies report a decrease in SERCA2a in heart failure, but none evaluate it's the role in early isolated diastolic dysfunction in supravalvular aortic stenosis (AoS). Our hypothesis was that SERCA2a participates in such dysfunction. Thirty-day-old male Wistar rats (60-80 g) were divided into AoS and Sham groups, which were submitted to surgery with or without aorta clipping, respectively...
April 13, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28421606/role-of-mucosa-in-generating-spontaneous-activity-in-the-guinea-pig-seminal-vesicle
#4
Mitsue Takeya, Hikaru Hashitani, Tokumasa Hayashi, Ryuhei Higashi, Kei-Ichiro Nakamura, Makoto Takano
The role of the mucosa in generating the spontaneous activity of guinea-pig seminal vesicle (SV) was explored. Changes in contractility, membrane potential and intracellular Ca(2+) dynamics of SV smooth muscle cells (SMCs) were recorded using isometric tension recording, intracellular microelectrode recording and epi-fluorescence Ca(2+) imaging, respectively. Mucosa-intact but not mucosa-denuded SV preparations generated TTX (1 μm)-resistant spontaneous phasic contractions that were abolished by nifedipine (3 μm)...
April 19, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28416809/perisomatic-changes-in-h-channels-regulate-depressive-behaviors-following-chronic-unpredictable-stress
#5
C S Kim, D H Brager, D Johnston
Chronic stress can be a precipitating factor in the onset of depression. Lentiviral-mediated knockdown of HCN1 protein expression and reduction of functional Ih produce antidepressant behavior. However, whether h-channels are altered in an animal model of depression is not known. We found that perisomatic HCN1 protein expression and Ih-sensitive physiological measurements were significantly increased in dorsal but not in ventral CA1 region/neurons following chronic unpredictable stress (CUS), a widely accepted model for major depressive disorder...
April 18, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28412648/content-decline-of-serca-inhibitors-saikosaponin-a-and-d-attenuates-cardiotoxicity-and-hepatotoxicity-of-vinegar-baked-radix-bupleuri
#6
Shifeng Wang, Yuxin Zhang, Qiao Zhang, Sha Peng, Chen Shen, Yangyang Yu, Minyu Zhang, Wei Yang, Qinghua Wu, Yanling Zhang, Shiyou Li, Yanjiang Qiao
Improper usage of unprocessed Radix bupleuri root (chaihu) may cause cardiotoxicity and liver injury. Baking herb with vinegar is believed to attenuate the adverse responses. However, the chemical and molecular basis involved remained unclear. To this end, we investigated the in vitro toxicity of saikosaponin a, c, d, and their hydrolysates saikosaponin b1 and b2. Results showed that SSa and SSd possessed higher affinity with sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) by molecular docking, and exhibited stronger toxic responses on cardiomyocytes and hepatocytes than the other three saikosaponins in equivalent concentrations...
April 4, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28404582/histone-deacetylase-activity-modulates-exercise-induced-skeletal-muscle-plasticity-in-zebrafish-danio-rerio
#7
Alec Izaac Marcus Simmonds, Frank Seebacher
Aerobic exercise has a positive impact on animals by enhancing skeletal muscle function and locomotor performance. Responses of skeletal muscle to exercise involve changes in energy metabolism, calcium handling, and the composition of contractile protein isoforms, which together influence contractile properties. Histone deacetylases (HDAC) can cause short-term changes in gene expression, and may thereby mediate plasticity in contractile properties of skeletal muscle in response to exercise. The aim of this project was to determine (in zebrafish, Danio rerio) the traits that mediate inter-individual differences in sustained and sprint performance, and to determine whether inhibiting class I and II HDACs mediates exercise-induced changes in these traits...
April 12, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28399403/thada-regulates-the-organismal-balance-between-energy-storage-and-heat-production
#8
Alexandra Moraru, Gulcin Cakan-Akdogan, Katrin Strassburger, Matilda Males, Sandra Mueller, Markus Jabs, Michael Muelleder, Martin Frejno, Bart P Braeckman, Markus Ralser, Aurelio A Teleman
Human susceptibility to obesity is mainly genetic, yet the underlying evolutionary drivers causing variation from person to person are not clear. One theory rationalizes that populations that have adapted to warmer climates have reduced their metabolic rates, thereby increasing their propensity to store energy. We uncover here the function of a gene that supports this theory. THADA is one of the genes most strongly selected during evolution as humans settled in different climates. We report here that THADA knockout flies are obese, hyperphagic, have reduced energy production, and are sensitive to the cold...
April 10, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28398363/-gene-therapy-in-heart-failure-the-unexpected-results-from-the-cupid-2-trial
#9
Marta Gigli, Gianfranco Sinagra, Luisa Mestroni
Heart failure is still a major cause of morbidity and mortality in Europe and North America. In the last three decades, gene therapy emerged as a target in the molecular mechanisms implicated in heart failure encouraging preclinical gene therapy studies in small and large animal models. Prior studies documented a decreased expression of sarcoplasmic reticulum Ca2+-ATPase protein (SERCA2a), a major cardiac calcium cycling protein, in heart failure. These results paved the way to preliminary studies based on gene transfer strategies of SERCA2a...
February 2017: Giornale Italiano di Cardiologia
https://www.readbyqxmd.com/read/28393439/effect-of-intracoronary-administration-of-aav1-serca2a-on-ventricular-remodelling-in-patients-with-advanced-systolic-heart-failure-results-from-the-agent-hf-randomized-phase-2-trial
#10
Jean-Sébastien Hulot, Joe-Elie Salem, Alban Redheuil, Jean-Philippe Collet, Shaida Varnous, Patrick Jourdain, Damien Logeart, Estelle Gandjbakhch, Claude Bernard, Stéphane N Hatem, Richard Isnard, Philippe Cluzel, Claude Le Feuvre, Pascal Leprince, Nadjib Hammoudi, François M Lemoine, David Klatzmann, Eric Vicaut, Michel Komajda, Gilles Montalescot, Anne-Marie Lompré, Roger J Hajjar
AIMS: Restoration of sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA2a) activity through gene transfer improved cardiac function in experimental and pilot studies in humans with heart failure. The AGENT-HF (NCT01966887) trial investigated the impact of adeno-associated virus (AAV1)/SERCA2a on ventricular remodelling using multimodality non-invasive cardiac imaging. METHODS AND RESULTS: AGENT-HF was a single centre, randomized, double-blind, placebo-controlled trial in adult patients with NYHA class III-IV ischaemic or non-ischaemic heart failure and left ventricular ejection fraction ≤35%...
April 10, 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/28384221/kchip2-regulates-the-cardiac-ca2-transient-and-myocyte-contractility-by-targeting-ryanodine-receptor-activity
#11
Drew M Nassal, Xiaoping Wan, Haiyan Liu, Kenneth R Laurita, Isabelle Deschênes
Pathologic electrical remodeling and attenuated cardiac contractility are featured characteristics of heart failure. Coinciding with these remodeling events is a loss of the K+ channel interacting protein, KChIP2. While, KChIP2 enhances the expression and stability of the Kv4 family of potassium channels, leading to a more pronounced transient outward K+ current, Ito,f, the guinea pig myocardium is unique in that Kv4 expression is absent, while KChIP2 expression is preserved, suggesting alternative consequences to KChIP2 loss...
2017: PloS One
https://www.readbyqxmd.com/read/28381328/long-term-effect-of-a-chronic-low-protein-multideficient-diet-on-the-heart-hypertension-and-heart-failure-in-chronically-malnourished-young-adult-rats
#12
Luiza V P Mendes, Sabrina R Gonsalez, Leonardo M Oliveira-Pinto, Amaury Pereira-Acácio, Christina M Takiya, José H M Nascimento, Marcelo Einicker-Lamas, Adalberto Vieyra, Valéria M N Cunha, Lucienne S Lara
BACKGROUND: We investigated whether a chronic low-protein multideficient diet (BRD) from weaning turns on cardiovascular adaptive responses that could culminate in hypertension and heart failure. METHODS AND RESULTS: Systolic pressure (SP) and heart rate (HR) were determined in CTRL (normal diet) and BRD rats. Plasma albumin, plasma urea and urinary urea excretion decreased in BRD rats. In this group, echocardiography and the Langendorff technique showed: (i) increased HR and hypertension; (ii) decreased LVDP, dP/dtmax, dP/dtmin, cardiac output, ejection fraction, stroke volume and left ventricular diameter...
March 27, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28380414/the-role-of-sirt1-in-diabetic-cardiomyopathy
#13
REVIEW
Hedyieh Karbasforooshan, Gholamreza Karimi
The prevalence of diabetes mellitus (DM) has been increasing worldwide. Diabetic cardiomyopathy (DCP) is the major risk for diabetes associated morbidity and mortality. Hyperglycemia and hyperinsulinemia play an indispensable role in underlying mechanisms of DCP. They increase advanced glycation end products (AGEs) following a series of events leading to myocardial damage and cardiomyopathy which include oxidative stress, increased inflammation, fibrosis, hypertrophy and apoptosis. SIRT1 is a nicotinamide adenosine dinucleotide (NAD)-dependent deacetylase that removes acetyl groups from proteins which can be implicated in DCP...
April 2, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28374834/glycation-of-paraoxonase-1-by-high-glucose-instigates-endoplasmic-reticulum-stress-to-induce-endothelial-dysfunction-in-vivo
#14
Wei Yu, Xiaoli Liu, Liru Feng, Hui Yang, Weiye Yu, Tiejian Feng, Shuangxi Wang, Jun Wang, Ning Liu
High-density lipoprotein (HDL) modulates low-density lipoprotein and cell membrane oxidation through the action of paraoxonase-1 (PON1). Endoplasmic reticulum (ER) stress has been linked to a wide range of human pathologies including diabetes, obesity, and atherosclerosis. Previous studies have reported that PON1 is glycated in diabetes. The aim of this study is to investigate whether and how PON1 glycation contributes to endothelial dysfunction in diabetes. ER stress markers were monitored by western blot...
April 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28374413/beneficial-effects-of-leptin-treatment-in-a-setting-of-cardiac-dysfunction-induced-by-transverse-aortic-constriction-in-mouse
#15
Nieves Gómez-Hurtado, Alejandro Domínguez-Rodríguez, Philippe Mateo, Maria Fernandez-Velasco, Almudena Val-Blasco, Rafael Aizpún, Jessica Sabourin, Ana Maria Gómez, Jean-Pierre Benitah, Carmen Delgado
KEY POINTS: Leptin, is a 16 kDa pleiotropic peptide, primary secreted by adipocytes, but also produced by other tissues including the heart. Controversy exists regarding the adverse and beneficial effects of Leptin on the heart We analysed the effect of a non-hypertensive dose of leptin on cardiac function, [Ca(2+) ]i handling and cellular electrophysiology, which participate in the genesis of pump failure and related arrhythmias both in control mice and in mice subjected to chronic pressure-overload by transverse aorta constriction We find that Leptin activates mechanisms that contribute to cardiac dysfunction in physiological conditions...
April 4, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28374038/preexisting-domain-motions-underlie-protonation-dependent-structural-transitions-of-the-p-type-ca-2-atpase
#16
Eli Fernández-de Gortari, L Michel Espinoza-Fonseca
We have performed microsecond molecular dynamics (MD) simulations to determine the mechanism for protonation-dependent structural transitions of the sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA), one of the most prominent members of the large P-type ATPase superfamily that transports ions across biological membranes. The release of two H(+) from the transport sites activates SERCA by inducing a structural transition between low (E2) and high (E1) Ca(2+)-affinity states (E2-to-E1 transition), but the structural mechanism by which transport site deprotonation facilitates this transition is unknown...
April 12, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28373957/comparative-study-the-expression-of-calcium-cycling-genes-in-bombay-duck-harpadon-nehereus-and-beltfish-trichiurus-lepturus-with-different-swimming-activities
#17
Hui Zhang, Gilbert Audira, Yuan Li, Weiwei Xian, Muhammed Muhsin Varikkodan, Chung-Der Hsiao
The contraction and relaxation events of the muscle is mediated by the coordination of many important calcium cycling proteins of ryanodine receptor (RYR), troponin C (TNNC), parvalbumin (PVALB), sarcoendoplasmic reticulum calcium transport ATPase (SERCA) and calsequestrin (CASQ). In higher vertebrates, the expression level of calcium cycling proteins are positively correlated to the muscle contraction/relaxation ability of the cell. In this study, we used RNAseq to explore the expression profile of calcium cycling genes between two marine fish of Bombay duck (Harpadon nehereus) and beltfish (Trichiurus lepturus) with poor and robust swimming activities, respectively...
June 2017: Genomics Data
https://www.readbyqxmd.com/read/28371485/target-deconvolution-efforts-on-wnt-pathway-screen-reveal-dual-modulation-of-oxidative-phosphorylation-and-serca2
#18
Matias Casas-Selves, Andrew Zhang, James E Dowling, Stefan Hallen, Aarti Kawatkar, Nicholas J Pace, Christopher Denz, Timothy Pontz, Farzin Garahdaghi, Qing Cao, Alan Sabirsh, Kumar Thakur, Nichole O'Connell, Jun Hu, Ivan Cornella-Taracido, Eranthie Weerapana, Michael Zinda, Robert A Goodnow
Wnt signaling is critical for development, cell proliferation and differentiation, and mutations in this pathway resulting in constitutive signaling have been implicated in various cancers. A pathway screen using a Wnt-dependent reporter identified a chemical series based on a 1,2,3-thiadiazole-5-carboxamide (TDZ) core with sub-M potency. We report here a comprehensive mechanism of action deconvolution study towards identifying the efficacy target(s) and biological implication of this chemical series involving bottom-up quantitative chemoproteomics, cell biology, and biochemical methods...
March 29, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28370799/through-modulation-of-cardiac-ca-2-handling-ucp2-affects-cardiac-electrophysiology-and-influences-the-susceptibility-for-ca-2-mediated-arrhythmias
#19
Robert Larbig, Sara Reda, Vera Paar, Andrea Trost, Johannes Leitner, Stephanie Weichselbaumer, Karolina A Motloch, Bernhard Wernly, Andreas Arrer, Benjamin Strauss, Michael Lichtenauer, Herbert A Reitsamer, Lars Eckardt, Guiscard Seebohm, Uta C Hoppe, Lukas J Motloch
Introduction UCP2 belongs to a superfamily of mitochondrial ion transporters. Due to its beneficial influence on production of reactive oxygen species it is suggested to reduce cardiac ischemic reperfusion injury. Recent studies uncovered its ability to regulate mitochondrial Ca(2+) -uptake and therefore to influence cardiac cytosolic Ca(2+) -handling, indicating compensatory pathways to avoid toxic Ca(2+) -overload in UCP2 knock-out mice (UCP2(-/-) ). However, the specific mechanisms and their impact on cardiac electrophysiology remain speculative...
March 31, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28329545/darier-white-disease
#20
Mitalee P Christman, Evan Reider, Randie H Kim, Nooshin Brinster, Elisa Femia, Miriam Keltz Pomeranz
We present a 58-year-old woman with bipolardisorder and with a longstanding history of yellowbrown,hyperkeratotic papules in a seborrheicdistribution and nail changes. Her father andpaternal grandmother had similar eruptions and alsohad psychiatric disease. Histopathologic examinationshowed acantholysis and dyskeratosis, which wasconsistent with Darier-White disease. Darier-Whitedisease is a rare, hereditary disorder that is inheritedin an autosomal dominant manner and that usuallypresents in adolescence or early adulthood dueto mutations in the SERCA2 calcium pump...
December 15, 2016: Dermatology Online Journal
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