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https://www.readbyqxmd.com/read/29914696/role-of-complement-c5a-and-histones-in-septic-cardiomyopathy
#1
Fatemeh Fattahi, Lynn M Frydrych, Guowu Bian, Miriam Kalbitz, Todd J Herron, Elizabeth A Malan, Matthew J Delano, Peter A Ward
Polymicrobial sepsis (after cecal ligation and puncture, CLP) causes robust complement activation with release of C5a. Many adverse events develop thereafter and will be discussed in this review article. Activation of complement system results in generation of C5a which interacts with its receptors (C5aR1, C5aR2). This leads to a series of harmful events, some of which are connected to the cardiomyopathy of sepsis, resulting in defective action potentials in cardiomyocytes (CMs), activation of the NLRP3 inflammasome in CMs and the appearance of extracellular histones, likely arising from activated neutrophils which form neutrophil extracellular traps (NETs)...
June 15, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29898361/the-intracellular-loop-of-the-na-ca2-exchanger-contains-an-awareness-ribbon-shaped-two-helix-bundle-domain
#2
Jiaqi Yuan, Chunhua Yuan, Mouzhe Xie, Lei Yu, Lei Bruschweiler-Li, Rafael Bruschweiler
The Na+/Ca2+ exchanger (NCX) is a ubiquitous single-chain membrane protein that plays a major role in regulating the intracellular Ca2+ homeostasis by the counter transport of Na+ and Ca2+ across the cell membrane. Other than its prokaryotic counterpart, which contains only the transmembrane domain and is self-sufficient as an active ion transporter, the eukaryotic NCX protein possesses in addition a large intracellular loop that senses intracellular calcium signals and controls the activation of ion transport across the membrane...
June 13, 2018: Biochemistry
https://www.readbyqxmd.com/read/29880193/%C3%AE-2-isoform-of-na-k-atpase-via-na-ca-2-exchanger-modulates-myelin-basic-protein-synthesis-in-oligodendrocyte-lineage-cells-in-vitro
#3
Jens Hammann, Davide Bassetti, Robin White, Heiko J Luhmann, Sergei Kirischuk
Oligodendrocytes in the CNS myelinate neuronal axons, facilitating rapid propagation of action potentials. Myelin basic protein (MBP) is an essential component of myelin and its absence results in severe hypomyelination. In oligodendrocyte lineage cell (OLC) monocultures MBP synthesis starts at DIV4. Ouabain (10 nM), a Na+ ,K+ -ATPase (NKA) blocker, stimulates MBP synthesis. As OLCs express the α2 isoform of NKA (α2-NKA) that has a high affinity for ouabain, we hypothesized that α2-NKA mediates this effect...
July 2018: Cell Calcium
https://www.readbyqxmd.com/read/29867966/autoantibodies-recognizing-secondary-necrotic-cells-promote-neutrophilic-phagocytosis-and-identify-patients-with-systemic-lupus-erythematosus
#4
Mona H C Biermann, Sebastian Boeltz, Elmar Pieterse, Jasmin Knopf, Jürgen Rech, Rostyslav Bilyy, Johan van der Vlag, Angela Tincani, Jörg H W Distler, Gerhard Krönke, Georg Andreas Schett, Martin Herrmann, Luis E Muñoz
Deficient clearance of apoptotic cells reportedly contributes to the etiopathogenesis of the autoimmune disease systemic lupus erythematosus (SLE). Based on this knowledge, we developed a highly specific and sensitive test for the detection of SLE autoantibodies (AAb) utilizing secondary NEcrotic cell (SNEC)-derived material as a substrate. The goal of the present study was to validate the use of SNEC as an appropriate antigen for the diagnosis of SLE in large cohort of patients. We confirmed the presence of apoptotically modified autoantigens on SNEC (dsDNA, high mobility group box 1 protein, apoptosis-associated chromatin modifications, e...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29788971/differential-regulation-of-nimodipine-sensitive-and-insensitive-ca-2-influx-by-the-na-ca-2-exchanger-and-mitochondria-in-the-rat-suprachiasmatic-nucleus-neurons
#5
Pi-Cheng Cheng, Yi-Chi Wang, Ya-Shuan Chen, Ruo-Ciao Cheng, Jyh-Jeen Yang, Rong-Chi Huang
BACKGROUND: Transmembrane Ca2+ influx is critical for molecular rhythmicity, metabolic activity, and neuropeptide release in the central clock of the suprachiasmatic nucleus (SCN). We previously reported that both the Na+ /Ca2+ exchanger (NCX) and mitochondria play a role in regulating intracellular Ca2+ homeostasis in the rat SCN neurons. Here we present evidence to show differential regulation by NCX and mitochondria of nimodipine-sensitive and -insensitive Ca2+ influx. METHODS: Ratiometric Ca2+ imaging was used to measure change in [Ca2+ ]i and patch clamp recordings to study spontaneous firing, membrane potential, and voltage-dependent Ca2+ channels in neurons from reduced SCN slice preparations...
May 22, 2018: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29738372/paradoxical-effects-of-sodium-calcium-exchanger-inhibition-on-torsade-de-pointes-and-early-afterdepolarization-in-a-heart-failure-rabbit-model
#6
Po-Cheng Chang, Yu-Ying Lu, Hui-Ling Lee, Shien-Fong Lin, Yen Chu, Ming-Shien Wen, Chung-Chuan Chou
Calcium homeostasis plays an important role in development of early afterdepolarizations (EADs) and torsade de pointes (TdP). The role of sodium-calcium exchanger (NCX) inhibition in genesis secondary Ca rise and EADs-TdP is still debated. Dual voltage and intracellular Ca optical mapping were conducted in 6 control and 9 failing rabbit hearts. After baseline electrophysiological and optical mapping studies, E4031 was given to simulate long QT syndrome. ORM-10103 was then administrated to examine the electrophysiological effects on EAD-TdP development...
May 3, 2018: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/29705719/calcium-and-atp-dependent-regulation-of-na-ca-exchange-function-in-bhk-cells-comparison-of-ncx1-and-ncx3-exchangers
#7
Vincenzo Lariccia, Salvatore Amoroso
Na+ /Ca2+ exchangers (NCX) mediate bidirectional Ca2+ fluxes across cell membranes and contribute to Ca2+ homeostasis in many cell types. Exchangers are regulated by gating reactions that depend on Na+ and Ca2+ binding to transport and regulatory sites. A Na+ i -dependent inactivation is prominent in all isoforms, whereas Ca2+ i -dependent regulation varies among isoforms. Here we characterize new details of NCX operation and describe differences and similarities between NCX3 and NCX1 regulation by intracellular Ca2+ and ATP...
July 2018: Cell Calcium
https://www.readbyqxmd.com/read/29705161/ca-2-entry-through-reverse-mode-na-ca-2-exchanger-contributes-to-store-operated-channel-mediated-neointima-formation-after-arterial-injury
#8
Bei Liu, Bin Zhang, Shiliang Huang, Lixia Yang, Carolyn M Roos, Michael A Thompson, Y S Prakash, Jie Zang, Jordan D Miller, Ruiwei Guo
BACKGROUND: Na+ /Ca2+ exchange (NCX) reversal-mediated Ca2+ entry is a critical pathway for stimulating proliferation in many cell lines. However, the role of reverse-mode NCX1 in neointima formation and atherosclerosis remains unclear. The aims of the present study were to investigate the functional role of NCX1 in the pathogenesis of atherosclerosis and vascular smooth muscle cell (VSMC) proliferation, and to determine the interaction between NCX1 and store depletion in VSMCs. METHODS: A rat balloon injury model was established to examine the effect of the knockdown of NCX1 on neointima formation after injury...
June 2018: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/29694879/positive-feedback-mechanisms-among-local-ca-releases-ncx-and-i-cal-ignite-pacemaker-action-potentials
#9
Alexey E Lyashkov, Joachim Behar, Edward G Lakatta, Yael Yaniv, Victor A Maltsev
No abstract text is available yet for this article.
April 24, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29679372/paraneoplastic-cerebellar-degeneration-yo-antibody-alters-mitochondrial-calcium-buffering-capacity
#10
D Panja, C A Vedeler, M Schubert
AIM: Neurodegeneration is associated with dysfunction of calcium buffering capacity and thereby sustained cellular and mitochondrial calcium overload. Paraneoplastic cerebellar degeneration (PCD), characterized by progressive Purkinje neurone degeneration following paraneoplastic Yo antibody internalization and binding to cerebellar degeneration-related protein CDR2 and CDR2L, has been linked to intracellular calcium homeostasis imbalance due to calbindin D28k malfunction. Therefore, we hypothesized that Yo antibody internalization affects not only calbindin calcium binding capacity, but also calcium-sensitive mitochondrial-associated signalling, causing mitochondrial calcium overload and thereby Purkinje neurone death...
April 21, 2018: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/29672298/intermittent-hypoxia-inhibits-na-h-exchange-mediated-acid-extrusion-via-intracellular-na-accumulation-in-cardiomyocytes
#11
Huai-Ren Chang, Chih-Feng Lien, Jing-Ren Jeng, Jen-Che Hsieh, Chen-Wei Chang, Jian-Hong Lin, Kun-Ta Yang
BACKGROUND/AIMS: Intermittent hypoxia (IH) has been shown to exert preconditioning-like cardioprotective effects. It also has been reported that IH preserves intracellular pH (pHi) during ischemia and protects cardiomyocytes against ischemic reperfusion injury. However, the exact mechanism is still unclear. METHODS: In this study, we used proton indicator BCECF-AM to analyze the rate of pHi recovery from acidosis in the IH model of rat neonatal cardiomyocytes. Neonatal cardiomyocytes were first treated with repetitive hypoxia-normoxia cycles for 1-4 days...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29669171/prostaglandin-analogues-and-nitric-oxide-contribution-in-the-treatment-of-ocular-hypertension-and-glaucoma
#12
REVIEW
Francesco Impagnatiello, Elena Bastia, Nicoletta Almirante, Stefania Brambilla, Brigitte Duquesroix, Angela C Kothe, Michael V W Bergamini
In patients with ocular hypertension or glaucoma, all treatments aim to lower intraocular pressure (IOP) by modulating aqueous humour (AH) production and/or uveoscleral and trabecular meshwork/Schlemm's canal AH drainage. PG analogues are considered to be the 'gold standard' treatment and are the most frequently used IOP-lowering agents. Recent data support an important role for NO in regulating IOP. Thus, novel PG analogues carrying a NO-donating moiety were recently advanced. Latanoprostene bunod (LBN) and NCX 470, NO-donating derivatives of latanoprost and bimatoprost, respectively, are examples of such compounds...
April 18, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29659148/hydrogen-sulphide-increases-pulmonary-veins-and-atrial-arrhythmogenesis-with-activation-of-protein-kinase-c
#13
Chao-Shun Chan, Yung-Kuo Lin, Yu-Hsun Kao, Yao-Chang Chen, Shih-Ann Chen, Yi-Jen Chen
Hydrogen sulphide (H2 S), one of the most common toxic air pollutants, is an important aetiology of atrial fibrillation (AF). Pulmonary veins (PVs) and left atrium (LA) are the most important AF trigger and substrate. We investigated whether H2 S may modulate the arrhythmogenesis of PVs and atria. Conventional microelectrodes and whole-cell patch clamp were performed in rabbit PV, sinoatrial node (SAN) or atrial cardiomyocytes before and after the perfusion of NaHS with or without chelerythrine (a selective PKC inhibitor), rottlerin (a specific PKC δ inhibitor) or KB-R7943 (a NCX inhibitor)...
April 16, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29649983/ncx-db-a-unified-resource-for-integrative-analysis-of-the-sodium-calcium-exchanger-super-family
#14
Katrin Bode, Damien M O'Halloran
Na+ /Ca2+ exchangers are low-affinity high-capacity transporters that mediate Ca2+ extrusion by coupling Ca2+ efflux to the influx of Na+ ions. The Na+ /Ca2+ exchangers form a super-family comprised of three branches each differing in ion-substrate selectivity: Na+ /Ca2+ exchangers (NCX), Na+ /Ca2+ /K+ exchangers, and Ca2+ /cation exchangers. Their primary function is to maintain Ca2+ homeostasis and play a particularly important role in excitable cells that experience transient Ca2+ fluxes. Research into the role and activity of Na+ /Ca2+ exchangers has focused extensively on the cardio-vascular system, however, growing evidence suggests that Na+ /Ca2+ exchangers play a key role in neuronal processes such as memory formation, learning, oligodendrocyte differentiation, neuroprotection during brain ischemia and axon guidance...
April 13, 2018: BMC Neuroscience
https://www.readbyqxmd.com/read/29625277/loss-of-p21-activated-kinase-1-pak1-promotes-atrial-arrhythmic-activity
#15
Jaime DeSantiago, Dan J Bare, Disha Varma, R John Solaro, Rishi Arora, Kathrin Banach
BACKGROUND: Atrial fibrillation (AF) is initiated through arrhythmic atrial excitation from outside the sinus node or remodeling of atrial tissue that allows reentry of excitation. Angiotensin II (AngII) has been implicated in the initiation and maintenance of AF through changes in Ca2+ handling and production of reactive oxygen species (ROS). OBJECTIVE: We aimed to determine the role of p21-activated kinase 1 (Pak1), a downstream target in the AngII signaling cascade, in atrial electrophysiology and arrhythmia...
April 3, 2018: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/29574129/activity-dependent-internalization-of-the-glutamate-transporter-glt-1-requires-calcium-entry-through-the-ncx-sodium-calcium-exchanger
#16
Ignacio Ibáñez, David Bartolomé-Martín, Dolores Piniella, Cecilio Giménez, Francisco Zafra
GLT-1 is the main glutamate transporter in the brain and its trafficking controls its availability at the cell surface, thereby shaping glutamatergic neurotransmission under physiological and pathological conditions. Extracellular glutamate is known to trigger ubiquitin-dependent GLT-1 internalization from the surface of the cell to the intracellular compartment, yet here we show that internalization also requires the participation of calcium ions. Consistent with previous studies, the addition of glutamate (1 mM) to mixed primary cultures (containing neurons and astrocytes) promotes GLT-1 internalization, an effect that was suppressed in the absence of extracellular Ca2+ ...
March 21, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29560783/trpc6-and-trpc4-heteromultimerization-mediates-store-depletion-activated-ncx1-reversal-in-proliferative-vascular-smooth-muscle-cells
#17
Bin Zhang, Bei Liu, Carolyn M Roos, Michael A Thompson, Y S Prakash, Jordan D Miller, Rui-Wei Guo
Store depletion has been shown to induce Ca2+ entry by Na+/Ca+ exchange (NCX) 1 reversal in proliferative vascular smooth muscle cells (VSMCs). The study objective was to investigate the role of transient receptor potential canonical (TRPC) channels in store depletion and NCX1 reversal in proliferative VSMCs. In cultured VSMCs, expressing TRPC1, TRPC4, and TRPC6, the removal of extracellular Na+ was followed by a significant increase of cytosolic Ca2+ concentration that was inhibited by KBR, a selective NCX1 inhibitor...
January 1, 2018: Channels
https://www.readbyqxmd.com/read/29551690/acute-and-long-term-ncx-activation-reduces-brain-injury-and-restores-behavioral-functions-in-mice-subjected-to-neonatal-brain-ischemia
#18
Pierpaolo Cerullo, Paola Brancaccio, Serenella Anzilotti, Antonio Vinciguerra, Ornella Cuomo, Ferdinando Fiorino, Beatrice Severino, Paola Di Vaio, Gianfranco Di Renzo, Lucio Annunziato, Giuseppe Pignataro
Hypoxic-ischemic encephalopathy (HI) accounts for the majority of developmental, motor and cognitive deficits in children, leading to life-long neurological impairments. Since the plasmamembrane sodium/calcium exchanger (NCX) plays a fundamental role in maintaining ionic homeostasis during adult brain ischemia, in the present work we aimed to demonstrate (1)the involvement of NCX in the pathophysiology of neonatal HI and (2)a possible NCX-based pharmacological intervention. HI was induced in neonatal mice at postnatal day 7(P7) by unilateral cut of the right common carotid artery, followed by 60 min exposure to 8%O2 ...
March 15, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29539403/positive-feedback-mechanisms-among-local-ca-releases-ncx-and-i-cal-ignite-pacemaker-action-potentials
#19
Alexey E Lyashkov, Joachim Behar, Edward G Lakatta, Yael Yaniv, Victor A Maltsev
Recent data suggest that cardiac pacemaker cell function is determined by numerous time-, voltage-, and Ca-dependent interactions of cell membrane electrogenic proteins (M-clock) and intracellular Ca cycling proteins (Ca-clock), forming a coupled-clock system. Many aspects of the coupled-clock system, however, remain underexplored. The key players of the system are Ca release channels (ryanodine receptors), generating local Ca releases (LCRs) from sarcoplasmic reticulum, electrogenic Na/Ca exchanger (NCX) current, and L-type Ca current (ICaL )...
March 13, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29531809/na-ca-2-exchanger-1-on-nuclear-envelope-controls-pten-akt-pathway-via-nucleoplasmic-ca-2-regulation-during-neuronal-differentiation
#20
Agnese Secondo, Alba Esposito, Tiziana Petrozziello, Francesca Boscia, Pasquale Molinaro, Valentina Tedeschi, Anna Pannaccione, Roselia Ciccone, Natascia Guida, Gianfranco Di Renzo, Lucio Annunziato
Nuclear envelope (NE) is a Ca2+ -storing organelle controlling neuronal differentiation through nuclear Ca2+ concentrations ([Ca2+ ]n ). However, how [Ca2+ ]n regulates this important function remains unknown. Here, we investigated the role of the nuclear form of the Na+ /Ca2+ exchanger 1(nuNCX1) during the different stages of neuronal differentiation and the involvement of PTEN/PI3'K/Akt pathway. In neuronal cells, nuNCX1 was detected on the inner membrane of the NE where protein expression and activity of the exchanger increased during NGF-induced differentiation...
December 2018: Cell Death Discovery
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