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https://www.readbyqxmd.com/read/29679372/paraneoplastic-cerebellar-degeneration-yo-antibody-alters-mitochondrial-calcium-buffering-capacity
#1
Debabrata Panja, Christian A Vedeler, Manja 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 neuron degeneration following paraneoplastic Yo antibody internalisation 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 internalisation affects not only calbindin calcium binding capacity but also calcium-sensitive mitochondrial-associated signalling, causing mitochondrial calcium overload and thereby Purkinje neuron 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
#2
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...
April 16, 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
#3
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 at lowering intraocular pressure (IOP) by modulating aqueous humor (AH) production and/or uveoscleral and trabecular meshwork /Schlemm's canal AH drainage. Prostaglandin (PG) analogues are considered the 'gold standard', and are the most frequently used IOP-lowering agents. Recent data support an important role of nitric oxide (NO) in regulating IOP. Thus novel PG analogues carrying a NO-donating moiety were recently advanced. Latanoprostene bunod (LBN) and NCX 470, respectively a NO-donating derivative of latanoprost and bimatoprost, 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
#4
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
#5
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/the-loss-of-p21-activated-kinase-pak1-promotes-atrial-arrhythmic-activity-the-role-of-pak1-in-atrial-arrhythmia
#6
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 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 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
#7
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
#8
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...
March 21, 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
#9
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
#10
Alexey E Lyashkov, Joachim Beahr, 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
#11
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
https://www.readbyqxmd.com/read/29526322/glycosylation-controls-sodium-calcium-exchanger-3-sub-cellular-localization-during-cell-cycle
#12
Tong Liu, Jian Zhao, Cristian Ibarra, Maxime U Garcia, Per Uhlén, Monica Nistér
The Na+ /Ca2+ exchanger (NCX) is a membrane antiporter that has been identified in the plasma membrane, the inner membrane of the nuclear envelope and in the membrane of the endoplasmic reticulum (ER). In humans, three genes have been identified, encoding unique NCX proteins. Although extensively studied, the NCX's sub-cellular localization and mechanisms regulating the activity of different subtypes are still ambiguous. Here we investigated the subcellular localization of the NCX subtype 3 (NCX3) and its impact on the cell cycle...
February 28, 2018: European Journal of Cell Biology
https://www.readbyqxmd.com/read/29518186/influence-of-long-term-salt-diets-on-cardiac-ca2-handling-and-contractility-proteins-in-hypertensive-rats
#13
Rebeca Caldeira Machado Berger, Acaris Benetti, Adriana Castello Costa Girardi, Ludimila Forechi, Rafaella Martins de Oliveira, Paula Frizera Vassallo, José Geraldo Mill
BACKGROUND: High sodium intake contributes to the pathogenesis of hypertension and adversely affects cardiac function. Conversely, sodium reduction is associated with a blood pressure decrease and improved cardiovascular function. However, the mechanisms that underlie the cardiac effects induced by salt intake in hypertension have not been fully elucidated. Ca2+ handling is critical for efficient myocardial function; thus, we aimed to investigate the long-term effects of diets with different salt contents on cardiac function and Ca2+ handling proteins in spontaneously hypertensive rats (SHRs)...
March 5, 2018: American Journal of Hypertension
https://www.readbyqxmd.com/read/29487533/sub-cellular-electrical-heterogeneity-revealed-by-loose-patch-recording-reflects-differential-localization-of-sarcolemmal-ion-channels-in-intact-rat-hearts
#14
Igor V Kubasov, Andrei Stepanov, Danila Bobkov, Przemysław B Radwanski, Maxim A Terpilowski, Maxim Dobretsov, Sandor Gyorke
The cardiac action potential (AP) is commonly recoded as an integral signal from isolated myocytes or ensembles of myocytes (with intracellular microelectrodes and extracellular macroelectrodes, respectively). These signals, however, do not provide a direct measure of activity of ion channels and transporters located in two major compartments of a cardiac myocyte: surface sarcolemma and the T-tubule system, which differentially contribute to impulse propagation and excitation-contraction (EC) coupling. In the present study we investigated electrical properties of myocytes within perfused intact rat heart employing loose patch recording with narrow-tip (2 μm diameter) extracellular electrodes...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29438213/new-no-donor-ncx-1443-therapeutic-effects-on-pulmonary-hypertension-in-the-sad-mouse-model-of-sickle-cell-disease
#15
Shariq Abid, Kanny Kebe, Amal Houssaïni, Françoise Tomberli, Elisabeth Marcos, Emilie Bizard, Marielle Breau, Aurelien Parpaleix, Claire-Marie Tissot, Bernard Maitre, Larissa Lipskaia, Genevieve Derumeaux, Elena Bastia, Armand Mekontso-Dessap, Serge Adnot
Nitric oxide (NO) donors may be useful for treating pulmonary hypertension (PH) complicating sickle cell disease (SCD), as endogenous NO is inactivated by hemoglobin released by intravascular hemolysis. Here, we investigated the effects of the new NO donor NCX1443 on PH in transgenic SAD mice, which exhibit mild SCD without severe hemolytic anemia. In SAD and wild-type (WT) mice, the pulmonary pressure response to acute hypoxia was similar and was abolished by 100 mg/kg NCX1443. The level of PH was also similar in SAD and WT mice exposed to chronic hypoxia (9% O2) alone or with SU5416, and was similarly reduced by daily NCX1443 gavage...
February 8, 2018: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/29344767/klotho-attenuates-isoproterenol-induced-hypertrophic-response-in-h9c2-cells-by-activating-na-k-atpase-and-inhibiting-the-reverse-mode-of-na-ca2-exchanger
#16
Gang Tang, Yi Shen, Pan Gao, Shuang-Shuang Song, Liang-Yi Si
Cardiac hypertrophy plays a major role in heart failure and is related to patient morbidity and mortality. Calcium overloading is a main risk for cardiac hypertrophy, and Na+/K+-ATPase (NKA) has been found that it could not only regulate intracellular Na+ levels but also control the intracellular Ca2+ ([Ca2+]i) level through Na+/Ca2+-exchanger (NCX). Recent studies have reported that klotho could affect [Ca2+]i level. In this study, we aimed at exploring the role of klotho in improving isoproterenol-induced hypertrophic response of H9C2 cells...
January 17, 2018: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/29331788/curcumin-inhibits-cardiac-hypertrophy-and-improves-cardiovascular-function-via-enhanced-na-ca-2-exchanger-expression-after-transverse-abdominal-aortic-constriction-in-rats
#17
Xiao-Jie Bai, Jun-Tao Hao, Jin Wang, Wei-Fang Zhang, Cai-Ping Yan, Jia-Hui Zhao, Zhi-Qing Zhao
BACKGROUND: This study tested the hypothesis that inhibition of cardiac hypertrophy and preservation of cardiac/endothelial function by the natural yellow pigment curcumin are associated with upregulated expression of Na+ /Ca2+ exchanger (NCX) after transverse aortic constriction (TAC). METHODS: Male Wistar rats were subjected to TAC for 10 weeks and curcumin (50 mg/kg/day) was fed by gastric gavage during TAC. Expression of NCX and endothelial nitric oxide synthase (eNOS) was analyzed by Western blot and immunohistochemistry...
February 2018: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29301861/molecular-determinants-of-ph-regulation-in-the-cardiac-na-ca-2-exchanger
#18
Scott John, Brian Kim, Riccardo Olcese, Joshua I Goldhaber, Michela Ottolia
The cardiac Na+ -Ca2+ exchanger (NCX) plays a critical role in the heart by extruding Ca2+ after each contraction and thus regulates cardiac contractility. The activity of NCX is strongly inhibited by cytosolic protons, which suggests that intracellular acidification will have important effects on heart contractility. However, the mechanisms underlying this inhibition remain elusive. It has been suggested that pH regulation originates from the competitive binding of protons to two Ca2+ -binding domains within the large cytoplasmic loop of NCX and requires inactivation by intracellular Na+ to fully develop...
February 5, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29274751/reduced-expression-of-na-ca-2-exchangers-is-associated-with-cognitive-deficits-seen-in-alzheimer-s-disease-model-mice
#19
Shigeki Moriguchi, Satomi Kita, Masahiro Fukaya, Makoto Osanai, Ryo Inagaki, Yuzuru Sasaki, Hisanao Izumi, Kyoji Horie, Junji Takeda, Takashi Saito, Hiroyuki Sakagami, Takaomi C Saido, Takahiro Iwamoto, Kohji Fukunaga
Na+ /Ca2+ exchangers (NCXs) are expressed primarily in the plasma membrane of most cell types, where they mediate electrogenic exchange of one Ca2+ for three Na+ ions, depending on Ca2+ and Na+ electrochemical gradients across the membrane. Three mammalian NCX isoforms (NCX1, NCX2, and NCX3) are each encoded by a distinct gene. Here, we report that NCX2 and NCX3 protein and mRNA levels are relatively reduced in hippocampal CA1 of APP23 and APP-KI mice. Likewise, NCX2+/- or NCX3+/- mice exhibited impaired hippocampal LTP and memory-related behaviors...
March 15, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29237756/the-prokaryotic-na-ca-2-exchanger-ncx_mj-transports-na-and-ca-2-in-a-3-1-stoichiometry
#20
Irina Shlosman, Fabrizio Marinelli, José D Faraldo-Gómez, Joseph A Mindell
Intracellular Ca2+ signals control a wide array of cellular processes. These signals require spatial and temporal regulation of the intracellular Ca2+ concentration, which is achieved in part by a class of ubiquitous membrane proteins known as sodium-calcium exchangers (NCXs). NCXs are secondary-active antiporters that power the translocation of Ca2+ across the cell membrane by coupling it to the flux of Na+ in the opposite direction, down an electrochemical gradient. Na+ and Ca2+ are translocated in separate steps of the antiport cycle, each of which is thought to entail a mechanism whereby ion-binding sites within the protein become alternately exposed to either side of the membrane...
January 2, 2018: Journal of General Physiology
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