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https://www.readbyqxmd.com/read/28424631/mechanisms-underlying-the-emergence-of-post-acidosis-arrhythmia-at-the-tissue-level-a-theoretical-study
#1
Jieyun Bai, Renli Yin, Kuanquan Wang, Henggui Zhang
Acidosis has complex electrophysiological effects, which are associated with a high recurrence of ventricular arrhythmias. Through multi-scale cardiac computer modeling, this study investigated the mechanisms underlying the emergence of post-acidosis arrhythmia at the tissue level. In simulations, ten Tusscher-Panfilov ventricular model was modified to incorporate various data on acidosis-induced alterations of cellular electrophysiology and intercellular electrical coupling. The single cell models were incorporated into multicellular one-dimensional (1D) fiber and 2D sheet tissue models...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28423119/importance-of-serca2a-on-early-isolated-diastolic-dysfunction-induced-by-supravalvular-aortic-stenosis-in-rats
#2
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/28414054/endothelium-dependent-vasorelaxant-effect-of-procyanidin-b2-on-human-internal-mammary-artery
#3
Aleksandra Novakovic, Marija Marinko, Goran Jankovic, Ivan Stojanovic, Predrag Milojevic, Dragoslav Nenezic, Vladimir Kanjuh, Qin Yang, Guo-Wei He
The aim of the present study was to investigate and characterize vasorelaxant effect of procyanidin B2 on human internal mammary artery (HIMA) as one of the mechanisms of its protective effect against vascular risk. Procyanidin B2 induced strong concentration-dependent relaxation of HIMA rings pre-contracted by phenylephrine. Pretreatment with L-NAME, a NO synthase inhibitor, hydroxocobalamin, a NO scavenger, and ODQ, an inhibitor of soluble guanylate cyclase, significantly inhibited procyanidin B2-induced relaxation of HIMA, while indomethacin, a cyclooxygenase inhibitor, considerably reduced effects of low concentrations...
April 13, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28412648/content-decline-of-serca-inhibitors-saikosaponin-a-and-d-attenuates-cardiotoxicity-and-hepatotoxicity-of-vinegar-baked-radix-bupleuri
#4
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/28410346/improved-survival-in-a-long-term-rat-model-of-sepsis-is-associated-with-reduced-mitochondrial-calcium-uptake-despite-increased-energetic-demand
#5
Bernardo B Pinto, Alex Dyson, Michele Umbrello, Jane E Carré, Cristiane Ritter, Innes Clatworthy, Michael R Duchen, Mervyn Singer
OBJECTIVES: To investigate the relationship between prognosis, changes in mitochondrial calcium uptake, and bioenergetic status in the heart during sepsis. DESIGN: In vivo and ex vivo controlled experimental studies. SETTING: University research laboratory. SUBJECTS: Male adult Wistar rats. INTERVENTIONS: Sepsis was induced by intraperitoneal injection of fecal slurry. Sham-operated animals served as controls...
April 13, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28410273/up-regulation-of-intracellular-calcium-handling-underlies-the-recovery-of-endotoxemic-cardiomyopathy-in-mice
#6
Justin C Morse, Joanne Huang, Natasha Khona, Edward J Miller, Deborah A Siwik, Wilson S Colucci, Ion A Hobai
BACKGROUND: In surviving patients, sepsis-induced cardiomyopathy is spontaneously reversible. In the absence of any experimental data, it is generally thought that cardiac recovery in sepsis simply follows the remission of systemic inflammation. Here the authors aimed to identify the myocardial mechanisms underlying cardiac recovery in endotoxemic mice. METHODS: Male C57BL/6 mice were challenged with lipopolysaccharide (7 μg/g, intraperitoneally) and followed for 12 days...
April 14, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28406633/probing-the-conformationally-excited-states-of-membrane-proteins-via-1-h-detected-mas-solid-state-nmr-spectroscopy
#7
T Gopinath, Sarah E D Nelson, Kailey J Soller, Gianluigi Veglia
Proteins exist in ensembles of conformational states that interconvert on various motional time scales. High-energy states of proteins, often referred to as conformationally excited states, are sparsely populated and have been found to play an essential role in many biological functions. However, detecting these states is quite difficult for conventional structural techniques. Recent progress in solution NMR spectroscopy made it possible to detect conformationally excited states in soluble proteins and characterize them at high resolution...
April 20, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28398363/-gene-therapy-in-heart-failure-the-unexpected-results-from-the-cupid-2-trial
#8
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/28390800/ca-2-release-via-two-pore-channel-type-2-tpc2-is-required-for-slow-muscle-cell-myofibrillogenesis-and-myotomal-patterning-in-intact-zebrafish-embryos
#9
Jeffrey J Kelu, Sarah E Webb, John Parrington, Antony Galione, Andrew L Miller
We recently demonstrated a critical role for two-pore channel type 2 (TPC2)-mediated Ca(2+) release during the differentiation of slow (skeletal) muscle cells (SMC) in intact zebrafish embryos, via the introduction of a translational-blocking morpholino antisense oligonucleotide (MO). Here, we extend our study and demonstrate that knockdown of TPC2 with a non-overlapping splice-blocking MO, knockout of TPC2 (via the generation of a tpcn2(dhkz1a) mutant line of zebrafish using CRISPR/Cas9 gene-editing), or the pharmacological inhibition of TPC2 action with bafilomycin A1 or trans-ned-19, also lead to a significant attenuation of SMC differentiation, characterized by a disruption of SMC myofibrillogenesis and gross morphological changes in the trunk musculature...
April 6, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28387457/dampened-activity-of-ryanodine-receptor-channels-in-mutant-skeletal-muscle-lacking-tric-a
#10
Sam El-Ajouz, Elisa Venturi, Katja Witschas, Matthew Beech, Abigail D Wilson, Chris Lindsay, David Eberhardt, Fiona O'Brien, Tsunaki Iida, Miyuki Nishi, Hiroshi Takeshima, Rebecca Sitsapesan
TRIC-A is a major component of the nuclear and sarcoplasmic reticulum (SR) membranes of cardiac and skeletal muscle, and is localised closely with RyR channels in the SR terminal cisternae. The skeletal muscle of Tric-a KO mice is characterised by Ca(2+) overloaded and swollen SR and by changes in the properties of SR Ca(2+) release. We therefore investigated if RyR1 gating behaviour is modified in the SR from Tric-a KO mice by incorporating native RyR1 into planar phospholipid bilayers under voltage-clamp conditions...
April 7, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28386464/the-microscopic-and-ultramicroscopic-changes-in-the-skeletal-muscles-caused-by-heavy-metal-salts
#11
REVIEW
Alexey Tymoshenko, Gennadii Tkach, Vitalii Sikora, Valentina Bumeister, Ihor Shpetnyi, Mykola Lyndin, Olena Maksymova, Anna Maslenko
PURPOSE: The article is devoted to study the structural changes in the skeletal muscles caused by heavy metal salts. MATERIALS AND METHODS: The study was conducted on 72 mature male rats. The experimental groups were given to drink water with combinations of heavy metal salts for one, two and three months. This type of water is typical for the water basins in the northern districts of the Sumy region. The study of morphological changes in the striated muscles was concluded using light and scanning electron microscopy...
June 1, 2016: Interventional Medicine & Applied Science
https://www.readbyqxmd.com/read/28369518/misregulation-of-calcium-handling-proteins-promotes-hyperactivation-of-calcineurin-nfat-signaling-in-skeletal-muscle-of-dm1-mice
#12
Aymeric Ravel-Chapuis, Guy Bélanger, Jocelyn Côté, Robin N Michel, Bernard J Jasmin
Myotonic Dystrophy type 1 (DM1) is caused by an expansion of CUG repeats in DMPK mRNAs. This mutation affects alternative splicing through misregulation of RNA-binding proteins. Amongst pre-mRNAs that are misspliced, several code for proteins involved in calcium homeostasis suggesting that calcium-handling and signaling are perturbed in DM1. Here, we analyzed expression of such proteins in DM1 mouse muscle. We found that the levels of several sarcoplasmic reticulum proteins (SERCA1, sarcolipin and calsequestrin) are altered, likely contributing to an imbalance in calcium homeostasis...
March 27, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28362405/local-field-fluorescence-microscopy-imaging-cellular-signals-in-intact-hearts
#13
Yuriana Aguilar-Sanchez, Diego Fainstein, Rafael Mejia-Alvarez, Ariel L Escobar
In the heart, molecular signaling studies are usually performed in isolated myocytes. However, many pathological situations such as ischemia and arrhythmias can only be fully understood at the whole organ level. Here, we present the spectroscopic technique of local field fluorescence microscopy (LFFM) that allows the measurement of cellular signals in the intact heart. The technique is based on a combination of a Langendorff perfused heart and optical fibers to record fluorescent signals. LFFM has various applications in the field of cardiovascular physiology to study the heart under normal and pathological conditions...
March 8, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28352365/heart-failure-modulates-electropharmacological-characteristics-of-sinoatrial-nodes
#14
Shih-Lin Chang, Hui-Lun Chuang, Yao-Chang Chen, Yu-Hsun Kao, Yung-Kuo Lin, Yung-Hsin Yeh, Shih-Ann Chen, Yi-Jen Chen
The impact of heart failure (HF) on sinoatrial node (SAN) channel regulation and electropharmacological responses has remained elusive. The present study aimed to investigate the effects of HF on the electrical activity of SANs with and without pharmacological interventions. Action potentials (APs) were recorded in isolated SANs from normal rabbits (control) and those with HF (rapid ventricular pacing for 4 weeks) prior to and after administration of a funny current blocker (ivabradine; 0.1, 0.3, 3 or 10 µM), a calmodulin kinase II inhibitor (KN-93; 0...
February 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28345618/ptpip51-regulates-mouse-cardiac-ischemia-reperfusion-through-mediating-the-mitochondria-sr-junction
#15
Xue Qiao, Shi Jia, Jingjing Ye, Xuan Fang, Chenglin Zhang, Yangpo Cao, Chunling Xu, Lifang Zhao, Yi Zhu, Lu Wang, Ming Zheng
Protein tyrosine phosphatase interacting protein 51 (PTPIP51) participates in multiple cellular processes, and dysfunction of PTPIP51 is implicated in diseases such as cancer and neurodegenerative disorders. However, there is no functional evidence showing the physiological or pathological roles of PTPIP51 in the heart. We have therefore investigated the role and mechanisms of PTPIP51 in regulating cardiac function. We found that PTPIP51 was markedly upregulated in ischemia/reperfusion heart. Upregulation of PTPIP51 by adenovirus-mediated overexpression markedly increased the contact of mitochondria-sarcoplasmic reticulum (SR), elevated mitochondrial Ca(2+) uptake from SR release through mitochondrial Ca(2+)uniporter...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28337975/a-chemical-chaperone-improves-muscle-function-in-mice-with-a-ryr1-mutation
#16
Chang Seok Lee, Amy D Hanna, Hui Wang, Adan Dagnino-Acosta, Aditya D Joshi, Mark Knoblauch, Yan Xia, Dimitra K Georgiou, Jianjun Xu, Cheng Long, Hisayuki Amano, Corey Reynolds, Keke Dong, John C Martin, William R Lagor, George G Rodney, Ergun Sahin, Caroline Sewry, Susan L Hamilton
Mutations in the RYR1 gene cause severe myopathies. Mice with an I4895T mutation in the type 1 ryanodine receptor/Ca(2+) release channel (RyR1) display muscle weakness and atrophy, but the underlying mechanisms are unclear. Here we show that the I4895T mutation in RyR1 decreases the amplitude of the sarcoplasmic reticulum (SR) Ca(2+) transient, resting cytosolic Ca(2+) levels, muscle triadin content and calsequestrin (CSQ) localization to the junctional SR, and increases endoplasmic reticulum (ER) stress/unfolded protein response (UPR) and mitochondrial ROS production...
March 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28337264/ip3r-and-ryr-calcium-channels-are-involved-in-neonatal-rat-cardiac-myocyte-hypertrophy-induced-by-tumor-necrosis-factor-%C3%AE
#17
Gui-Jun Wang, Lian-Yi Guo, Hong-Xin Wang, Yu-Sheng Yao
To investigate which calcium channels are involved in cardiac myocyte hypertrophy induced by TNF-α, cultured cardiomyocytes were treated with 100 μg/L TNF-α. In addition, three different calcium channel blockers (2-APB, ryanodine and nifedipine) were used, and the effects of each calcium channel blocker on cardiac hypertrophy induced by TNF-α were carefully observed. Measurements included cytosolic calcium transients ([Ca(2+)]i), the level of intracellular calcium in individual cells, cell protein content, cell protein synthesis and cell volume...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28336810/role-of-transient-receptor-potential-vanilloid-1-trpv1-in-the-modulation-of-airway-smooth-muscle-tone-and-calcium-handling
#18
Gene T Yocum, Jun Chen, Christine H Choi, Elizabeth A Townsend, Yi Zhang, Dingbang Xu, Xiao Wen Fu, Michael J Sanderson, Charles W Emala
Asthma is a common disorder characterized, in part, by airway smooth muscle (ASM) hyperresponsiveness. Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel expressed on airway nerve fibers that modulates afferent signals resulting in cough, and potentially bronchoconstriction. In the present study, the TRPV1 transcript was detected by RT-PCR in primary cultured human ASM cells, and the TRPV1 protein was detected in ASM of human trachea by immunohistochemistry. Proximity ligation assays suggest that TRPV1 is expressed in the sarcoplasmic reticulum membrane of human ASM cells in close association with sarco/endoplasmic reticulum Ca2+ ATPase 2...
March 23, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28332558/multiple-h-sensors-mediate-the-extracellular-acidification-induced-ca-2-i-elevation-in-cultured-rat-ventricular-cardiomyocytes
#19
Yuan-Lang Hu, Xue Mi, Chao Huang, Hui-Fang Wang, Jian-Ren Song, Qing Shu, Lan Ni, Jian-Guo Chen, Fang Wang, Zhuang-Li Hu
Acidosis has been known to cause "Ca(2+) transients", however, the mechanism is still uncertain. Here, we demonstrated that multiple H(+) sensors, such as ASICs, TRPV1 and proton-sensing G protein coupled receptors (GPCRs) are involved in extracellular acidification-induced intracellular calcium ([Ca(2+)]i) elevation. By using calcium imaging measures, we observed that both ASIC and TRPV1 channels inhibitors suppressed the [Ca(2+)]i elevation induced by extracellular acidosis in cultured rat cardiac myocytes...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332202/calcium-signalling-silencing-in-atrial-fibrillation
#20
Maura Greiser
Sub-cellular calcium signalling silencing is a novel and distinct cellular and molecular adaptive response to rapid cardiac activation. Calcium signalling silencing develops during short-term sustained rapid atrial activation as seen clinically during paroxysmal atrial fibrillation (AF). It is the first 'anti-arrhythmic' adaptive response in the setting of AF and appears to counteract the maladaptive changes that lead to intracellular Ca(2+) signalling instability and Ca(2+) based arrhythmogenicity. Calcium signalling silencing results in a failed propagation of the [Ca(2+) ]i signal to the myocyte centre in both patients with AF and in a rabbit model...
March 22, 2017: Journal of Physiology
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