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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
#1
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
#2
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-ca2-exchanger-expression-after-transverse-abdominal-aortic-constriction-in-rats
#3
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...
July 15, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29301861/molecular-determinants-of-ph-regulation-in-the-cardiac-na-ca2-exchanger
#4
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...
January 4, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29274751/reduced-expression-of-na-ca2-exchangers-is-associated-with-cognitive-deficits-seen-in-alzheimer-s-disease-model-mice
#5
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...
December 22, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29237756/the-prokaryotic-na-ca2-exchanger-ncx_mj-transports-na-and-ca2-in-a-3-1-stoichiometry
#6
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...
December 13, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/29217667/critical-contribution-of-na-ca2-exchanger-to-the-ca2-mediated-vasodilation-activated-in-endothelial-cells-of-resistance-arteries
#7
Mauricio A Lillo, Pablo S Gaete, Mariela Puebla, Nicolás M Ardiles, Inés Poblete, Alvaro Becerra, Felipe Simon, Xavier F Figueroa
Na+-Ca2+ exchanger (NCX) contributes to control the intracellular free Ca2+ concentration ([Ca2+]i), but the functional activation of NCX reverse mode (NCXrm) in endothelial cells is controversial. We evaluated the participation of NCXrm-mediated Ca2+ uptake in the endothelium-dependent vasodilation of rat isolated mesenteric arterial beds. In phenylephrine-contracted mesenteries, the acetylcholine (ACh)-induced vasodilation was abolished by treatment with the NCXrm blockers SEA0400, KB-R7943, or SN-6. Consistent with that, the ACh-induced hyperpolarization observed in primary cultures of mesenteric endothelial cells and in smooth muscle of isolated mesenteric resistance arteries was attenuated by KB-R7943 and SEA0400, respectively...
December 7, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29212769/functional-and-structural-characterization-of-a-novel-malignant-hyperthermia-susceptible-variant-of-dhpr-%C3%AE-1a-subunit-cacnb1
#8
Claudio F Perez, Jose M Eltit, Jose R Lopez, Dóra Bodnár, Angela F Dulhunty, Shouvik Aditya, Marco G Casarotto
Malignant Hyperthermia (MH) susceptibility has been recently linked to a novel variant of β1a subunit of the dihydropyridine receptor (DHPR), a channel essential for Ca2+ regulation in skeletal muscle. Here we evaluate the effect of the mutant variant V156A on the structure/function of DHPR β1a subunit and assess its role on Ca2+ metabolism of cultured myotubes. Using differential scanning fluorimetry we show that mutation V156A causes a significant reduction in thermal stability of the Src homology 3 (SH3)/Guanylate Kinase (GK) core domain of β1a subunit...
December 6, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29192360/hyperglycemia-induced-cardiac-contractile-dysfunction-in-the-diabetic-heart
#9
REVIEW
Raphael M Singh, Tahreem Waqar, Frank C Howarth, Ernest Adeghate, Keshore Bidasee, Jaipaul Singh
The development of a diabetic cardiomyopathy is a multifactorial process, and evidence is accumulating that defects in intracellular free calcium concentration [Ca2+]i or its homeostasis are related to impaired mechanical performance of the diabetic heart leading to a reduction in contractile dysfunction. Defects in ryanodine receptor, reduced activity of the sarcoplasmic reticulum calcium pump (SERCA) and, along with reduced activity of the sodium-calcium exchanger (NCX) and alterations in myofilament, collectively cause a calcium imbalance within the diabetic cardiomyocytes...
December 1, 2017: Heart Failure Reviews
https://www.readbyqxmd.com/read/29158789/arecoline-increases-glycolysis-and-modulates-ph-regulator-expression-in-ha22t-vgh-hepatoma-cells-leading-to-increase-of-intracellular-ca-2-reactive-oxygen-species-and-anoikis
#10
Hsiao-Ling Cheng, Wen-Tsan Chang, Yu-Chen Hu, Bau-Shan Hsieh, Tzu-Ching Huang, Inn-Wen Chong, Li-Wen Huang, Kee-Lung Chang
Background: Cancer cells proliferate rapidly and are resistant to cell death, relying on aggravated glycolysis to satisfy their increased demand for energy and biosynthetic precursors. However, this process may create unfavorable microenvironments, such as increased acidity, leading to cytotoxicity. Our previous study demonstrated that arecoline induces anoikis of HA22T/VGH hepatoma cells. The present study aimed to examine if arecoline induced anoikis is related to the glycolytic pathway and explore the underlying mechanisms...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29155350/the-pmca-pumps-in-genetically-determined-neuronal-pathologies
#11
REVIEW
Tito Calì, Marisa Brini, Ernesto Carafoli
Ca(2+) signals regulate most aspects of animal cell life. They are of particular importance to the nervous system, in which they regulate specific functions, from neuronal development to synaptic plasticity. The homeostasis of cell Ca(2+) must thus be very precisely regulated: in all cells Ca(2+) pumps transport it from the cytosol to the extracellular medium (the Plasma Membrane Ca(2+) ATPases, hereafter referred to as PMCA pumps) or to the lumen of intracellular organelles (the Sarco/Endoplasmatic Reticulum Ca(2+) ATPase and the Secretory Pathway Ca(2+) ATPase, hereafter referred to as SERCA and SPCA pumps, respectively)...
November 16, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29152764/comparative-transcriptome-analysis-of-the-calcium-signaling-and-expression-analysis-of-sodium-calcium-exchanger-in-aspergillus-cristatus
#12
Xiu-Xiu Ren, Yuchen Wang, YongXiang Liu, Yumei Tan, Chunguang Ren, Yongyi Ge, Zuoyi Liu
Aspergillus cristatus develops into various stages under different Na concentrations: the sexual stage in 0.5 M NaCl and asexual development stage in 3 M NaCl. In order to explore whether the Ca(2+) signaling pathway in A. cristatus responded to the changes in the salt stress, we analyzed the gene expression levels in A. cristatus respectively cultured in 0.5 M NaCl and 3 M NaCl. According to the BLAST analysis results, we identified 25 Ca(2+) -signaling proteins in A. cristatus. The expression levels of most genes involved in the Ca(2+) -signaling pathway in A...
November 20, 2017: Journal of Basic Microbiology
https://www.readbyqxmd.com/read/29136153/reverse-ncx-attenuates-cellular-sodium-loading-in-metabolically-compromised-cortex
#13
Niklas J Gerkau, Cordula Rakers, Simone Durry, Gabor C Petzold, Christine R Rose
In core regions of ischemic stroke, disruption of blood flow causes breakdown of ionic gradients and, ultimately, calcium overload and cell death. In the surrounding penumbra, cells may recover upon reperfusion, but recovery is hampered by additional metabolic demands imposed by peri-infarct depolarizations (PIDs). There is evidence that sodium influx drives PIDs, but no data exist on PID-related sodium accumulations in vivo. Here, we found that PIDs in mouse neocortex are associated with propagating sodium elevations in neurons and astrocytes...
November 9, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29133913/nitric-oxide-mediated-inhibition-of-antigen-presentation-from-dcs-to-cd4-t-cells-in-cancer-and-measurement-of-stat1-nitration
#14
Joseph Markowitz, Jiang Wang, Zach Vangundy, Jia You, Vedat Yildiz, Lianbo Yu, Isaac P Foote, Owen E Branson, Andrew R Stiff, Taylor R Brooks, Brandon Biesiadecki, Thomas Olencki, Susheela Tridandapani, Michael A Freitas, Tracey Papenfuss, Mitch A Phelps, William E Carson
Myeloid derived suppressor cells (MDSC) produce nitric oxide (NO) and inhibit dendritic cell (DC) immune responses in cancer. DCs present cancer cell antigens to CD4(+) T cells through Jak-STAT signal transduction. In this study, NO donors (SNAP and DETA-NONOate) inhibited DC antigen presentation. As expected, MDSC isolated from peripheral blood mononuclear cells (PBMC) from cancer patients produced high NO levels. We hypothesized that NO producing MDSC in tumor-bearing hosts would inhibit DC antigen presentation...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29117223/sensitivity-analysis-revealing-the-effect-of-modulating-ionic-mechanisms-on-calcium-dynamics-in-simulated-human-heart-failure
#15
Maria T Mora, Jose M Ferrero, Lucia Romero, Beatriz Trenor
Abnormal intracellular Ca2+ handling is the major contributor to the depressed cardiac contractility observed in heart failure. The electrophysiological remodeling associated with this pathology alters both the action potential and the Ca2+ dynamics, leading to a defective excitation-contraction coupling that ends in mechanical dysfunction. The importance of maintaining a correct intracellular Ca2+ concentration requires a better understanding of its regulation by ionic mechanisms. To study the electrical activity and ionic homeostasis of failing myocytes, a modified version of the O'Hara et al...
2017: PloS One
https://www.readbyqxmd.com/read/29112392/solid-versus-solution-spin-crossover-and-the-importance-of-the%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-fe-n%C3%A2-c-x-angle
#16
Santiago Rodríguez-Jiménez, Sally Brooker
A new family of mononuclear [Fe(II)(Rdpt)2(NCE)2] complexes (E = S, Se, or BH3) is formed by 1:2 reaction of [Fe(II)(pyridine)4(NCE)2] with the monotopic pyridyl triazole ligand 4-(4-methylphenyl)-3-(2-pyridinyl)-5-phenyl-4H-1,2,4-triazole (tolpyph). The three complexes are obtained as six different solvatomorphs: [Fe(II)(tolpyph)2(NCS)2]·H2O (1·H2O), 1·1.5CH3OH·0.5H2O, [Fe(II)(tolpyph)2(NCSe)2] (2), 2·1.5H2O, [Fe(II)(tolpyph)2(NCBH3)2] (3), and 3·H2O. Single-crystal X-ray diffraction reveals that 1·1...
November 7, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/29066415/inotropic-effect-of-ncx-inhibition-depends-on-the-relative-activity-of-the-reverse-ncx-assessed-by-a-novel-inhibitor-orm-10962-on-canine-ventricular-myocytes
#17
Kinga Oravecz, Anita Kormos, Andrea Gruber, Zoltán Márton, Zsófia Kohajda, Leila Mirzaei, Norbert Jost, Jouko Levijoki, Piero Pollesello, Tuula Koskelainen, Leena Otsomaa, András Tóth, Julius Gy Papp, Péter P Nánási, Gudrun Antoons, András Varró, Károly Acsai, Norbert Nagy
Na(+)/Ca(2+) exchanger (NCX) is the main Ca(2+) transporter in cardiac myocytes. Its inhibition could be expected to exert positive inotropic action by accumulation of cytosolic Ca(2+) ([Ca(2+)]i). However, we have observed only a marginal positive inotropic effect upon selective inhibition of NCX, which was enhanced when forward activity was facilitated. Here we attempted to clarify the underlying mechanism of the limited inotropic action of selective NCX inhibition by a novel inhibitor ORM-10962 on canine ventricular myocytes...
October 21, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29055103/mitochondrial-ca-2-dynamics-in-cells-and-suspensions
#18
Benjamin Wacquier, Hugo E Romero C, Virginia González-Vélez, Laurent Combettes, Geneviève Dupont
Mitochondria play a significant role in shaping cytosolic Ca(2+) signals. Thus, Ca(2+) transfers across the mitochondrial membrane are much studied, not only in intact cells but also in artificial systems such as mitochondrial suspensions or permeabilised cells. Observed rates of Ca(2+) changes vary by at least one order of magnitude. In this work, we investigate the relationship between the Ca(2+) dynamics observed in various experimental conditions using a computational model calibrated on experimental data...
October 21, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29048915/chiral-and-racemic-spin-crossover-polymorphs-in-a-family-of-mononuclear-iron-ii-compounds
#19
Carlos Bartual-Murgui, Lucía Piñeiro-López, F Javier Valverde-Muñoz, M Carmen Muñoz, Maksym Seredyuk, José Antonio Real
Understanding the origin of cooperativity and the equilibrium temperature of transition (T1/2) displayed by the spin-crossover (SCO) compounds as well as controlling these parameters are of paramount importance for future applications. For this task, the occurrence of polymorphism, presented by a number of SCO complexes, may provide deep insight into the influence of the supramolecular organization on the SCO behavior. In this context, herein we present a novel family of mononuclear octahedral Fe(II) complexes with formula cis-[Fe(bqen)(NCX)2], where bqen is the chelating tetradentate ligand N,N'-bis(8-quinolyl)ethane-1,2-diamine and X = S, Se...
November 6, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/29026150/essential-role-of-the-na-ca2-exchanger-ncx-in-glutamate-enhanced-cell-survival-in-cardiac-cells-exposed-to-hypoxia-reoxygenation
#20
Marta Maiolino, Pasqualina Castaldo, Vincenzo Lariccia, Silvia Piccirillo, Salvatore Amoroso, Simona Magi
Myocardial ischemia culminates in ATP production impairment, ionic derangement and cell death. The provision of metabolic substrates during reperfusion significantly increases heart tolerance to ischemia by improving mitochondrial performance. Under normoxia, glutamate contributes to myocardial energy balance as substrate for anaplerotic reactions, and we demonstrated that the Na(+)/Ca(2+) exchanger1 (NCX1) provides functional support for both glutamate uptake and use for ATP synthesis. Here we investigated the role of NCX1 in the potential of glutamate to improve energy metabolism and survival of cardiac cells subjected to hypoxia/reoxygenation (H/R)...
October 12, 2017: Scientific Reports
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