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https://www.readbyqxmd.com/read/28181690/calcium-mediated-cellular-triggered-activity-in-atrial-fibrillation
#1
Dobromir Dobrev, Xander H T Wehrens
Although atrial fibrillation (AF) is the most commonly encountered cardiac arrhythmia, the basic mechanisms underlying this disorder remain incompletely understood. During the past decade or so, it has become clear that alterations in intracellular Ca(2+) handling may play a role in the pathogenesis of AF. Studies in small and large animal models, as well as atrial samples from patients with different forms of AF have implicated ryanodine receptor type 2 (RyR2) dysfunction and enhanced spontaneous Ca(2+) release events from the sarcoplasmic reticulum (SR) as a potential cause of proarrhythmic cellular ectopic (triggered) activity in AF...
February 9, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28181072/interactions-of-mitochondria-metabolism-and-calcium-regulation-in-alzheimer-s-disease-a-calcinist-point-of-view
#2
Gary E Gibson, Ankita Thakkar
Decades of research suggest that alterations in calcium are central to the pathophysiology of Alzheimer's Disease (AD). Highly reproducible changes in calcium dynamics occur in cells from patients with both genetic and non-genetic forms of AD relative to controls. The most robust change is an exaggerated release of calcium from internal stores. Detailed analysis of these changes in animal and cell models of the AD-causing presenilin mutations reveal robust changes in ryanodine receptors, inositol tris-phosphate receptors, calcium leak channels and store activated calcium entry...
February 8, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28179072/orai3-channel-is-the-2-apb-induced-endoplasmic-reticulum-calcium-leak
#3
Daniel Leon-Aparicio, Jonathan Pacheco, Jesus Chavez-Reyes, Jose M Galindo, Jesus Valdes, Luis Vaca, Agustin Guerrero-Hernandez
We have studied in HeLa cells the molecular nature of the 2-APB induced ER Ca(2+) leak using synthetic Ca(2+) indicators that report changes in both the cytoplasmic ([Ca(2+)]i) and the luminal ER ([Ca(2+)]ER) Ca(2+) concentrations. We have tested the hypothesis that Orai channels participate in the 2-APB-induced ER Ca(2+) leak that was characterized in the companion paper. The expression of the dominant negative Orai1 E106A mutant, which has been reported to block the activity of all three types of Orai channels, inhibited the effect of 2-APB on the [Ca(2+)]ER but did not decrease the ER Ca(2+) leak after thapsigargin (TG)...
January 23, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28169003/increased-calcium-leak-associated-with-reduced-calsequestrin-expression-in-hyperthyroid-cardiomyocytes
#4
David R de Alba-Aguayo, Natalia Pavón, Martha Mercado-Morales, Miyamin Miranda-Saturnino, Mavil López-Casamichana, Agustin Guerrero-Hernández, Angelica Rueda
INTRODUCTION: Calcium (Ca(2+)) leak during cardiac diastole is chiefly mediated by intracellular Ca(2+) channel/Ryanodine Receptors. Increased diastolic Ca(2+) leak has been proposed as the mechanism underlying the appearance of hereditary arrhythmias. However, little is known about alterations in diastolic Ca(2+) leak and the specific roles played by key intracellular Ca(2+)-handling proteins in hyperthyroidism, a known arrhythmogenic condition. AIM: We sought to determine whether there were modifications in diastolic Ca(2+) leak, based on the recording of Ca(2+) sparks and Ca(2+) waves; we also investigated changes in the expression and activity of key Ca(2+) handling proteins, including ryanodine receptors, Sarco-Endoplasmic Reticulum Ca(2+) ATPase pump and calsequestrin in isolated left-ventricular cardiomyocytes isolated from hyperthyroid rats...
January 23, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28144998/p2y12-receptors-in-primary-microglia-activate-nuclear-factor-of-activated-t-cell-signaling-to-induce-c-c-chemokine-3-expression
#5
Hidetoshi Tozaki-Saitoh, Hiroyuki Miyata, Tomohiro Yamashita, Katsuyuki Matsushita, Makoto Tsuda, Kazuhide Inoue
Microglia are widely accepted as surveillants in the central nervous system that are continually searching the local environment for signs of injury. Following an inflammatory situation, microglia alter their morphology, extend ramified processes, and undergo cell body hypertrophy. Extracellular nucleotides are recognized as a danger signal by microglia. ADP acting on P2Y12 receptors induce process extension of microglia thereby attracting microglia to the site of adenosine tri-phosphate/ADP leaking or release...
January 31, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28116867/pass-the-rock-calcium-the-achilles-heel-of-transcatheter-valve-replacement
#6
EDITORIAL
James M McCabe, Larry S Dean
Increasing annular calcification portends more adverse outcomes and worse hemodynamic results following percutaneous structural heart interventions. Though the Direct Flow prosthesis did not appear to have significantly different post-procedural gradients based on aortic valve calcium burden in a selected group of patients, the average residual gradients were relatively high in all cases and the presence of a paravalvular leak was more common with increasing valvular calcification. It is unclear how the Direct Flow prosthesis fits into the armamentarium of TAVR prostheses...
January 2017: Catheterization and Cardiovascular Interventions
https://www.readbyqxmd.com/read/28105734/calcium-calmodulin-dependent-protein-kinase-mediates-the-intracellular-signaling-pathways-of-cardiac-apoptosis-in-mice-with-impaired-glucose-tolerance
#7
Marilen Federico, Enrique L Portiansky, Leandro Sommese, Francisco J Alvarado, Paula G Blanco, Carolina N Zanuzzi, John Dedman, Marcia Kaetzel, Xander H T Wehrens, Alicia Mattiazzi, Julieta Palomeque
Background The impact of cardiac apoptosis in pre-diabetic stages of diabetic cardiomyopathy is unknown. We described that myocytes from fructose-rich diet (FRD) animals exhibit arrhythmias produced by exacerbated Ca(2+) /calmodulin-protein kinase (CaMKII) activity, ryanodine receptors (RyR2) phosphorylation and sarcoplasmic reticulum (SR) Ca(2+) leak. We tested the hypothesis that this mechanism also underlies cardiac apoptosis in pre-diabetes. Methods and Results We generated a pre-diabetic model in mice fed with FRD...
January 20, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28077389/enhanced-oxidative-capacity-of-ground-squirrel-brain-mitochondria-during-hibernation
#8
Mallory A Ballinger, Christine Schwartz, Matthew T Andrews
During hibernation, thirteen-lined ground squirrels (Ictidomys tridecemlineatus) regularly cycle between bouts of torpor and interbout arousal (IBA).  Most of the brain is electrically quiescent during torpor, but regains activity quickly upon arousal to IBA resulting in extreme oscillations in energy demand during hibernation.  We predicted increased functional capacity of brain mitochondria during hibernation compared to spring to accommodate the variable energy demands of hibernation.  To address this hypothesis, we examined mitochondrial bioenergetics in the ground squirrel brain across three time points: spring (SP), torpor (TOR), and IBA...
January 11, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/27942915/treatment-of-hand-enchondroma-with-injectable-calcium-phosphate-cement-a-series-of-eight-cases
#9
Mohammad Al Rajeh, Juan José Hidalgo Diaz, Sybille Facca, Anne Sophie Matheron, Stéphanie Gouzou, Philippe Liverneaux
The gold standard treatment for enchondroma in the hand is curettage and filling of the defect. The goal of this study was to evaluate the results when injectable calcium phosphate cement is used to fill the bone defect. Eight patients having a mean age of 44 years were operated through a minimally invasive skin incision. After a small bone window was made, curettage of the lesion was performed and verified by intraosseous endoscopy. The defect was filled with injectable calcium phosphate cement (JectOS/AREX(®)BONE, Kasios, L'Union France)...
February 2017: European Journal of Orthopaedic Surgery & Traumatology: Orthopédie Traumatologie
https://www.readbyqxmd.com/read/27824546/citrullination-in-rheumatoid-arthritis-a-process-promoted-by-neutrophil-lysis
#10
REVIEW
Tal Gazitt, Christian Lood, Keith B Elkon
Anti-citrullinated protein antibodies (ACPAs) are highly specific serologic markers for rheumatoid arthritis (RA) and can pre-date clinical disease onset by up to 10 years, also predicting erosive disease. The process of citrullination, the post-translational conversion of arginine to citrulline residues, is mediated by peptidylarginine deiminase (PAD) enzymes present in polymorphonuclear cells (PMNs). Calcium ions (Ca(2+)) are required for PAD activation, but the intracellular Ca(2+) concentration in normal cells is much lower than the optimal Ca(2+) concentration needed for PAD activation...
October 31, 2016: Rambam Maimonides Medical Journal
https://www.readbyqxmd.com/read/27784668/muscle-as-an-osteoinductive-niche-for-local-bone-formation-with-the-use-of-a-biphasic-calcium-sulphate-hydroxyapatite-biomaterial
#11
D B Raina, A Gupta, M M Petersen, W Hettwer, M McNally, M Tägil, M-H Zheng, A Kumar, L Lidgren
OBJECTIVES: We have observed clinical cases where bone is formed in the overlaying muscle covering surgically created bone defects treated with a hydroxyapatite/calcium sulphate biomaterial. Our objective was to investigate the osteoinductive potential of the biomaterial and to determine if growth factors secreted from local bone cells induce osteoblastic differentiation of muscle cells. MATERIALS AND METHODS: We seeded mouse skeletal muscle cells C2C12 on the hydroxyapatite/calcium sulphate biomaterial and the phenotype of the cells was analysed...
October 2016: Bone & Joint Research
https://www.readbyqxmd.com/read/27760856/high-throughput-screens-to-discover-small-molecule-modulators-of-ryanodine-receptor-calcium-release-channels
#12
Robyn T Rebbeck, Maram M Essawy, Florentin R Nitu, Benjamin D Grant, Gregory D Gillispie, David D Thomas, Donald M Bers, Razvan L Cornea
Using time-resolved fluorescence resonance energy transfer (FRET), we have developed and validated the first high-throughput screening (HTS) method to discover compounds that modulate an intracellular Ca(2+) channel, the ryanodine receptor (RyR), for therapeutic applications. Intracellular Ca(2+) regulation is critical for striated muscle function, and RyR is a central player. At resting [Ca(2+)], an increased propensity of channel opening due to RyR dysregulation is associated with severe cardiac and skeletal myopathies, diabetes, and neurological disorders...
October 19, 2016: Journal of Biomolecular Screening
https://www.readbyqxmd.com/read/27648519/calcium-calmodulin-protein-kinase-ii-dependent-ryanodine-receptor-phosphorylation-mediates-cardiac-contractile-dysfunction-associated-with-sepsis
#13
Marisa Sepúlveda, Luis A Gonano, Manuel Viotti, Malena Morell, Paula Blanco, Micaela López Alarcón, Isalira Peroba Ramos, Adriana Bastos Carvalho, Emiliano Medei, Martín Vila Petroff
OBJECTIVES: Sepsis is associated with cardiac contractile dysfunction attributed to alterations in Ca handling. We examined the subcellular mechanisms involved in sarcoplasmic reticulum Ca loss that mediate altered Ca handling and contractile dysfunction associated with sepsis. DESIGN: Randomized controlled trial. SETTING: Research laboratory SUBJECTS:: Male wild type and transgenic mice INTERVENTIONS:: We induced sepsis in mice using the colon ascendens stent peritonitis model...
September 19, 2016: Critical Care Medicine
https://www.readbyqxmd.com/read/27641664/dysregulation-of-neuronal-calcium-homeostasis-in-alzheimer-s-disease-a-therapeutic-opportunity
#14
REVIEW
Elena Popugaeva, Ekaterina Pchitskaya, Ilya Bezprozvanny
Alzheimer's disease (AD) is the disease of lost memories. Synaptic loss is a major reason for memory defects in AD. Signaling pathways involved in memory loss in AD are under intense investigation. The role of deranged neuronal calcium (Ca(2+)) signaling in synaptic loss in AD is described in this review. Familial AD (FAD) mutations in presenilins are linked directly with synaptic Ca(2+) signaling abnormalities, most likely by affecting endoplasmic reticulum (ER) Ca(2+) leak function of presenilins. Excessive ER Ca(2+) release via type 2 ryanodine receptors (RyanR2) is observed in AD spines due to increase in expression and function of RyanR2...
February 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27626620/the-emerging-role-of-calmodulin-regulation-of-ryr2-in-controlling-heart-rhythm-the-progression-of-heart-failure-and-the-antiarrhythmic-action-of-dantrolene
#15
Kafa Walweel, Ye Win Oo, Derek R Laver
Cardiac output and rhythm depend on the release and the take-up of calcium from the sarcoplasmic reticulum (SR). Excessive diastolic calcium leak from the SR due to dysfunctional calcium release channels (RyR2) contributes to the formation of delayed after-depolarizations, which underlie the fatal arrhythmias that occur in heart failure and inherited syndromes. Calmodulin (CaM) is a calcium-binding protein that regulates target proteins and acts as a calcium sensor. CaM is comprised of two calcium-binding EF-hand domains and a flexible linker...
January 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27587534/single-stage-treatment-of-chronic-osteomyelitis-with-a-new-absorbable-gentamicin-loaded-calcium-sulphate-hydroxyapatite-biocomposite-a-prospective-series-of-100-cases
#16
M A McNally, J Y Ferguson, A C K Lau, M Diefenbeck, M Scarborough, A J Ramsden, B L Atkins
AIMS: Chronic osteomyelitis may recur if dead space management, after excision of infected bone, is inadequate. This study describes the results of a strategy for the management of deep bone infection and evaluates a new antibiotic-loaded biocomposite in the eradication of infection from bone defects. PATIENTS AND METHODS: We report a prospective study of 100 patients with chronic osteomyelitis, in 105 bones. Osteomyelitis followed injury or surgery in 81 patients...
September 2016: Bone & Joint Journal
https://www.readbyqxmd.com/read/27446973/-a-small-leak-will-sink-a-great-ship-hypoxia-inducible-factor-and-group-iii-pulmonary-hypertension
#17
Andrew J Bryant, Edward W Scott
Pulmonary hypertension complicating idiopathic pulmonary fibrosis, also known as secondary pulmonary hypertension, represents a major source of morbidity and mortality in affected patients. While the study of primary pulmonary arterial hypertension has yielded several therapies, the same is not true for the treatment of pulmonary hypertension secondary to pulmonary fibrosis. Recent studies have indicated an important role of hypoxia-inducible factor (HIF) - a regulatory protein that is vital in adaptation to hypoxic conditions - in the development of secondary pulmonary hypertension...
2016: Receptors & Clinical Investigation
https://www.readbyqxmd.com/read/27318036/camkii-dependent-phosphorylation-of-ryr2-promotes-targetable-pathological-ryr2-conformational-shift
#18
Hitoshi Uchinoumi, Yi Yang, Tetsuro Oda, Na Li, Katherina M Alsina, Jose L Puglisi, Ye Chen-Izu, Razvan L Cornea, Xander H T Wehrens, Donald M Bers
Diastolic calcium (Ca) leak via cardiac ryanodine receptors (RyR2) can cause arrhythmias and heart failure (HF). Ca/calmodulin (CaM)-dependent kinase II (CaMKII) is upregulated and more active in HF, promoting RyR2-mediated Ca leak by RyR2-Ser2814 phosphorylation. Here, we tested a mechanistic hypothesis that RyR2 phosphorylation by CaMKII increases Ca leak by promoting a pathological RyR2 conformation with reduced CaM affinity. Acute CaMKII activation in wild-type RyR2, and phosphomimetic RyR2-S2814D (vs. non-phosphorylatable RyR2-S2814A) knock-in mouse myocytes increased SR Ca leak, reduced CaM-RyR2 affinity, and caused a pathological shift in RyR2 conformation (detected via increased access of the RyR2 structural peptide DPc10)...
September 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27245055/hepatocyte-nuclear-factor-4-alfa-mutation-associated-with-hyperinsulinaemic-hypoglycaemia-and-atypical-renal-fanconi-syndrome-expanding-the-clinical-phenotype
#19
Nicola Improda, Pratik Shah, Maria Güemes, Clare Gilbert, Kate Morgan, Neil Sebire, Detlef Bockenhauer, Khalid Hussain
BACKGROUND: The p.R63W mutation in the hepatocyte nuclear factor-4 alpha (HNF4A) results in macrosomia and atypical Fanconi syndrome, in addition to hyperinsulinaemic hypoglycaemia (HI). We describe 2 infants carrying this mutation, presenting with additional features. Cases Series: Patient 1, a male born with a birth weight of 1.7 SDS, was diagnosed with HI on day 2 of life. He responded to 3-10 mg/kg/day of diazoxide. Raised serum creatinine led to the investigation of renal tubular function, showing leaking of electrolytes and protein...
2016: Hormone Research in Pædiatrics
https://www.readbyqxmd.com/read/27154230/mitochondrial-oxidative-stress-during-cardiac-lipid-overload-causes-intracellular-calcium-leak-and-arrhythmia
#20
Leroy C Joseph, Prakash Subramanyam, Christopher Radlicz, Chad M Trent, Vivek Iyer, Henry M Colecraft, John P Morrow
BACKGROUND: Diabetes and obesity are associated with an increased risk of arrhythmia and sudden cardiac death. Abnormal lipid accumulation is observed in cardiomyocytes of obese and diabetic patients, which may contribute to arrhythmia, but the mechanisms are poorly understood. A transgenic mouse model of cardiac lipid overload, the peroxisome proliferator-activated receptor-γ (PPARg) cardiac overexpression mouse, has long QT and increased ventricular ectopy. OBJECTIVE: The purpose of this study was to evaluate the hypothesis that the increase in ventricular ectopy during cardiac lipid overload is caused by abnormalities in calcium handling due to increased mitochondrial oxidative stress...
August 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
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