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Academic literature on the topic 'Orai1'

Author: Grafiati
Published: 4 June 2021
Last updated: 1 June 2024

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Journal articles on the topic "Orai1"

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Eckstein, Miriam, Martin Vaeth, Francisco J. Aulestia, Veronica Costiniti, Serena N. Kassam, Timothy G. Bromage, Pal Pedersen, et al. "Differential regulation of Ca2+ influx by ORAI channels mediates enamel mineralization." Science Signaling 12, no. 578 (April 23, 2019): eaav4663. http://dx.doi.org/10.1126/scisignal.aav4663.

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Store-operated Ca2+ entry (SOCE) channels are highly selective Ca2+ channels activated by the endoplasmic reticulum (ER) sensors STIM1 and STIM2. Their direct interaction with the pore-forming plasma membrane ORAI proteins (ORAI1, ORAI2, and ORAI3) leads to sustained Ca2+ fluxes that are critical for many cellular functions. Mutations in the human ORAI1 gene result in immunodeficiency, anhidrotic ectodermal dysplasia, and enamel defects. In our investigation of the role of ORAI proteins in enamel, we identified enamel defects in a patient with an ORAI1 null mutation. Targeted deletion of the Orai1 gene in mice showed enamel defects and reduced SOCE in isolated enamel cells. However, Orai2−/− mice showed normal enamel despite having increased SOCE in the enamel cells. Knockdown experiments in the enamel cell line LS8 suggested that ORAI2 and ORAI3 modulated ORAI1 function, with ORAI1 and ORAI2 being the main contributors to SOCE. ORAI1-deficient LS8 cells showed altered mitochondrial respiration with increased oxygen consumption rate and ATP, which was associated with altered redox status and enhanced ER Ca2+ uptake, likely due to S-glutathionylation of SERCA pumps. Our findings demonstrate an important role of ORAI1 in Ca2+ influx in enamel cells and establish a link between SOCE, mitochondrial function, and redox homeostasis.
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Jardin, Isaac, Alejandro Berna-Erro, Joel Nieto-Felipe, Alvaro Macias, Jose Sanchez-Collado, Jose J. Lopez, Gines M. Salido, and Juan A. Rosado. "Similarities and Differences between the Orai1 Variants: Orai1α and Orai1β." International Journal of Molecular Sciences 23, no. 23 (November 23, 2022): 14568. http://dx.doi.org/10.3390/ijms232314568.

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Orai1, the first identified member of the Orai protein family, is ubiquitously expressed in the animal kingdom. Orai1 was initially characterized as the channel responsible for the store-operated calcium entry (SOCE), a major mechanism that allows cytosolic calcium concentration increments upon receptor-mediated IP3 generation, which results in intracellular Ca2+ store depletion. Furthermore, current evidence supports that abnormal Orai1 expression or function underlies several disorders. Orai1 is, together with STIM1, the key element of SOCE, conducting the Ca2+ release-activated Ca2+ (CRAC) current and, in association with TRPC1, the store-operated Ca2+ (SOC) current. Additionally, Orai1 is involved in non-capacitative pathways, as the arachidonate-regulated or LTC4-regulated Ca2+ channel (ARC/LRC), store-independent Ca2+ influx activated by the secretory pathway Ca2+-ATPase (SPCA2) and the small conductance Ca2+-activated K+ channel 3 (SK3). Furthermore, Orai1 possesses two variants, Orai1α and Orai1β, the latter lacking 63 amino acids in the N-terminus as compared to the full-length Orai1α form, which confers distinct features to each variant. Here, we review the current knowledge about the differences between Orai1α and Orai1β, the implications of the Ca2+ signals triggered by each variant, and their downstream modulatory effect within the cell.
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Liang, Ch, and F. Wu. "Reconstitution of calcium channel protein Orai3 into liposomes for functional studies." Биохимия 88, no. 9 (December 15, 2023): 1570–80. http://dx.doi.org/10.31857/s0320972523090099.

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Store-operated calcium entry (SOCE) is the main mechanism for the Ca2+ influx in non-excitable cells. The two major components of SOCE are stromal interaction molecule 1 (STIM1) in the endoplasmic reticulum and Ca2+ release-activated Ca2+ channel (CRAC) Orai on the plasma membrane. SOCE requires interaction between STIM1 and Orai. Mammals have three Orai homologs: Orai1, Orai2, and Orai3. Although Orai1 has been widely studied and proven to be essential for numerous cellular processes, Orai3 has also attracted a significant attention recently. The gating and activation mechanisms of Orai3 have yet to be fully elucidated. Here, we expressed, purified, and reconstituted Orai3 protein into liposomes and investigated its orientation and oligomeric state in the resulting proteoliposomes. STIM1 interacted with the Orai3-containing proteoliposomes and mediated calcium release from them, suggesting that the Orai3 channel was functional and that recombinant STIM1 could directly open the Orai3 channel in vitro. The developed in vitro calcium release system could be used to study the structure, function, and pharmacology of Orai3 channel.
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Fresquez, Adriana M., and Carl White. "Extracellular cysteines C226 and C232 mediate hydrogen sulfide-dependent inhibition of Orai3-mediated store-operated calcium entry." American Journal of Physiology-Cell Physiology 322, no. 1 (January 1, 2022): C38—C48. http://dx.doi.org/10.1152/ajpcell.00490.2019.

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The gaseous signaling molecule hydrogen sulfide (H2S) physiologically regulates store-operated Ca2+ entry (SOCE). The SOCE machinery consists of the plasma membrane-localized Orai channels (Orai1-3) and endoplasmic reticulum-localized stromal interaction molecule (STIM)1 and STIM2 proteins. H2S inhibits Orai3- but not Orai1- or Orai2-mediated SOCE. The current objective was to define the mechanism by which H2S selectively modifies Orai3. We measured SOCE and STIM1/Orai3 dynamics and interactions in HEK293 cells exogenously expressing fluorescently tagged human STIM1 and Orai3 in the presence and absence of the H2S donor GYY4137. Two cysteines (C226 and C232) are present in Orai3 that are absent in the Orai1 and Orai2. When we mutated either of these cysteines to serine, alone or in combination, SOCE inhibition by H2S was abolished. We also established that inhibition was dependent on an interaction with STIM1. To further define the effects of H2S on STIM1/Orai3 interaction, we performed a series of fluorescence recovery after photobleaching (FRAP), colocalization, and fluorescence resonance energy transfer (FRET) experiments. Treatment with H2S did not affect the mobility of Orai3 in the membrane, nor did it influence STIM1/Orai3 puncta formation or STIM1-Orai3 protein-protein interactions. These data support a model in which H2S modification of Orai3 at cysteines 226 and 232 limits SOCE evoked upon store depletion and STIM1 engagement, by a mechanism independent of the interaction between Orai3 and STIM1.
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Smyth, Jeremy T., and James W. Putney. "Regulation of store-operated calcium entry during cell division." Biochemical Society Transactions 40, no. 1 (January 19, 2012): 119–23. http://dx.doi.org/10.1042/bst20110612.

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Store-operate Ca2+ channels gate Ca2+ entry into the cytoplasm in response to the depletion of Ca2+ from endoplasmic reticulum Ca2+ stores. The major molecular components of store-operated Ca2+ entry are STIM (stromal-interacting molecule) 1 (and in some instances STIM2) that serves as the endoplasmic reticulum Ca2+ sensor, and Orai (Orai1, Orai2 and Orai3) which function as pore-forming subunits of the store-operated channel. It has been known for some time that store-operated Ca2+ entry is shut down during cell division. Recent work has revealed complex mechanisms regulating the functions and locations of both STIM1 and Orai1 in dividing cells.
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Grimes, Derayvia, Ryan Johnson, Madeline Pashos, Celeste Cummings, Chen Kang, Georgia R. Sampedro, Eric Tycksen, et al. "ORAI1 and ORAI2 modulate murine neutrophil calcium signaling, cellular activation, and host defense." Proceedings of the National Academy of Sciences 117, no. 39 (September 14, 2020): 24403–14. http://dx.doi.org/10.1073/pnas.2008032117.

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Calcium signals are initiated in immune cells by the process of store-operated calcium entry (SOCE), where receptor activation triggers transient calcium release from the endoplasmic reticulum, followed by opening of plasma-membrane calcium-release activated calcium (CRAC) channels. ORAI1, ORAI2, and ORAI3 are known to comprise the CRAC channel; however, the contributions of individual isoforms to neutrophil function are not well understood. Here, we show that loss of ORAI1 partially decreases calcium influx, while loss of both ORAI1 and ORAI2 completely abolishes SOCE. In other immune-cell types, loss of ORAI2 enhances SOCE. In contrast, we find that ORAI2-deficient neutrophils display decreased calcium influx, which is correlated with measurable differences in the regulation of neutrophil membrane potential via KCa3.1. Decreased SOCE in ORAI1-, ORAI2-, and ORAI1/2-deficient neutrophils impairs multiple neutrophil functions, including phagocytosis, degranulation, leukotriene, and reactive oxygen species (ROS) production, rendering ORAI1/2-deficient mice highly susceptible to staphylococcal infection. This study demonstrates that ORAI1 and ORAI2 are the primary components of the neutrophil CRAC channel and identifies subpopulations of neutrophils where cell-membrane potential functions as a rheostat to modulate the SOCE response. These findings have implications for mechanisms that modulate neutrophil function during infection, acute and chronic inflammatory conditions, and cancer.
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Tiffner, Adéla, and Isabella Derler. "Isoform-Specific Properties of Orai Homologues in Activation, Downstream Signaling, Physiology and Pathophysiology." International Journal of Molecular Sciences 22, no. 15 (July 27, 2021): 8020. http://dx.doi.org/10.3390/ijms22158020.

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Ca2+ ion channels are critical in a variety of physiological events, including cell growth, differentiation, gene transcription and apoptosis. One such essential entry pathway for calcium into the cell is the Ca2+ release-activated Ca2+ (CRAC) channel. It consists of the Ca2+ sensing protein, stromal interaction molecule 1 (STIM1) located in the endoplasmic reticulum (ER) and a Ca2+ ion channel Orai in the plasma membrane. The Orai channel family includes three homologues Orai1, Orai2 and Orai3. While Orai1 is the “classical” Ca2+ ion channel within the CRAC channel complex and plays a universal role in the human body, there is increasing evidence that Orai2 and Orai3 are important in specific physiological and pathophysiological processes. This makes them an attractive target in drug discovery, but requires a detailed understanding of the three Orai channels and, in particular, their differences. Orai channel activation is initiated via Ca2+ store depletion, which is sensed by STIM1 proteins, and induces their conformational change and oligomerization. Upon STIM1 coupling, Orai channels activate to allow Ca2+ permeation into the cell. While this activation mechanism is comparable among the isoforms, they differ by a number of functional and structural properties due to non-conserved regions in their sequences. In this review, we summarize the knowledge as well as open questions in our current understanding of the three isoforms in terms of their structure/function relationship, downstream signaling and physiology as well as pathophysiology.
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Zhang, Xuexin, Ping Xin, Ryan E. Yoast, Scott M. Emrich, Martin T. Johnson, Trayambak Pathak, J. Cory Benson, et al. "Distinct pharmacological profiles of ORAI1, ORAI2, and ORAI3 channels." Cell Calcium 91 (November 2020): 102281. http://dx.doi.org/10.1016/j.ceca.2020.102281.

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Baryshnikov, Sergey G., Maria V. Pulina, Alessandra Zulian, Cristina I. Linde, and Vera A. Golovina. "Orai1, a critical component of store-operated Ca2+ entry, is functionally associated with Na+/Ca2+ exchanger and plasma membrane Ca2+ pump in proliferating human arterial myocytes." American Journal of Physiology-Cell Physiology 297, no. 5 (November 2009): C1103—C1112. http://dx.doi.org/10.1152/ajpcell.00283.2009.

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Ca2+ entry through store-operated channels (SOCs) in the plasma membrane plays an important role in regulation of vascular smooth muscle contraction, tone, and cell proliferation. The C-type transient receptor potential (TRPC) channels have been proposed as major candidates for SOCs in vascular smooth muscle. Recently, two families of transmembrane proteins, Orai [also known as Ca2+ release-activated Ca2+ channel modulator (CRACM)] and stromal interacting molecule 1 (STIM1), were shown to be essential for the activation of SOCs mainly in nonexcitable cells. Here, using small interfering RNA, we show that Orai1 plays an essential role in activating store-operated Ca2+ entry (SOCE) in primary cultured proliferating human aortic smooth muscle cells (hASMCs), whereas Orai2 and Orai3 do not contribute to SOCE. Knockdown of Orai1 protein expression significantly attenuated SOCE. Moreover, inhibition of Orai1 downregulated expression of Na+/Ca2+ exchanger type 1 (NCX1) and plasma membrane Ca2+ pump isoform 1 (PMCA1). The rate of cytosolic free Ca2+ concentration decay after Ca2+ transients in Ca2+-free medium was also greatly decreased under these conditions. This reduction of Ca2+ extrusion, presumably via NCX1 and PMCA1, may be a compensation for the reduced SOCE. Immunocytochemical observations indicate that Orai1 and NCX1 are clustered in plasma membrane microdomains. Cell proliferation was attenuated in hASMCs with disrupted Orai1 expression and reduced SOCE. Thus Orai1 appears to be a critical component of SOCE in proliferating vascular smooth muscle cells, and may therefore be a key player during vascular growth and remodeling.
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Liu, Xiaoling, Tianyuan Zheng, Yan Jiang, Lei Wang, Yuchen Zhang, Qiyu Liang, and Yuejie Chen. "Molecular Mechanism Analysis of STIM1 Thermal Sensation." Cells 12, no. 22 (November 12, 2023): 2613. http://dx.doi.org/10.3390/cells12222613.

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STIM1 has been identified as a new warm sensor, but the exact molecular mechanism remains unclear. In this study, a variety of mutants of STIM1, Orai1 and Orai3 were generated. The single–cell calcium imaging and confocal analysis were used to evaluate the thermal sensitivity of the resulting STIM mutants and the interaction between STIM1 and Orai mutants in response to temperature. Our results suggested that the CC1–SOAR of STIM1 was a direct activation domain of temperature, leading to subsequent STIM1 activation, and the transmembrane (TM) region and K domain but not EF–SAM were needed for this process. Furthermore, both the TM and SOAR domains exhibited similarities and differences between STIM1–mediated thermal sensation and store–operated calcium entry (SOCE), and the key sites of Orai1 showed similar roles in these two responses. Additionally, the TM23 (comprising TM2, loop2, and TM3) region of Orai1 was identified as the key domain determining the STIM1/Orai1 thermal response pattern, while the temperature reactive mode of STIM1/Orai3 seemed to result from a combined effect of Orai3. These findings provide important support for the specific molecular mechanism of STIM1–induced thermal response, as well as the interaction mechanism of STIM1 with Orai1 and Orai3 after being activated by temperature.
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Dissertations / Theses on the topic "Orai1"

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Röther, Jens. "Die Rolle von Orai1 in der Entwicklung und Aktivierung von T- und B- Lymphozyten und die Bedeutung von Mutationen in Orai1 für die Pathogenese schwerer kombinierter Immundefekte." Doctoral thesis, Universitätsbibliothek Leipzig, 2011. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-70949.

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Ein durch „Ca2+ Release Activated Ca2+ (CRAC)“-Kanal vermittelter Ca2+-Einstrom ist unverzichtbar für die vollständige Aktivierung von T-Zellen und eine produktive Immunantwort. Im Jahr 2006 führte die Entdeckung des transmembranen Proteins Orai1, einer porenbildenden Untereinheit des CRAC-Kanals, zu einem besseren Verständnis dieses Signalweges. Eine Mutation in Orai1 hat durch die Aufhebung der CRAC-Kanal Funktion eine schwere kombinierte Immundefizienz (SCID) zur Folge (Feske, S. et al. 2006). Die im Rahmen dieser Arbeit präsentierten Experimente hatten die nähere Erforschung der Rolle von Orai1 in Bezug auf die Aktivierung und Entwicklung von Lymphozyten sowie auf die pathogenetische Bedeutung für humane Immundefektsyndrome zum Ziel. So konnte hier durch das Sequenzieren genomischer DNA mehrerer SCID-Patienten eine neue Mutation in Orai1 aufgedeckt werden. Mithilfe intrazellulärer Durchflusszytometrie und Real-Time-PCR gelang es, die Expression von Orai1 auf humanen und murinen Immunzellen, einschließlich T- und B-Lymphozyten, nachzuweisen. Darüber hinaus wurden Orai1 „knock-in“ Mäuse analysiert, welche transgen für eine bei zwei SCID-Patienten gefundene Mutation (R91W) (Feske, S. et al. 2006) sind. Dadurch war es möglich die Funktion von Orai1 und die des CRAC-Kanal vermittelten Ca2+-Einstroms für die Entwicklung und Aktivierung von Lymphozyten zu analysieren. Diese transgenen Mäuse stellen das zu diesem Zeitpunkt erste Tiermodell dar, mit dessen Hilfe die Rolle von CRAC-Kanälen in vivo studiert werden kann.
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Jensen, Drake. "Functional Analysis of Calmodulin's Calcium Dependent Inactivation of Orai1." Thesis, Southern Illinois University at Edwardsville, 2015. http://pqdtopen.proquest.com/#viewpdf?dispub=1589551.

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Calmodulin (CaM) plays an important role in calcium (Ca2+)-dependent signal transduction. Ca2+ binding to CaM triggers a conformational change, forming a hydrophobic patch that is important for target protein recognition. CaM regulates a Ca2+-dependent inactivation (CDI) process in store-operated Ca2+ entry (SOCE), by interacting with the N-terminus of the hexameric plasma membrane Ca2+ channel Orai1. To understand the relationship between Ca2+-induced hydrophobicity of CaM and the CaM/Orai interaction, chimera proteins constructed by exchanging EF-hands of CaM with those of Troponin C (TnC) were used as an informative probe to better understand the functionality of each EF-hand. ANS was used to assess the context of the induced hydrophobic surface on CaM and chimeras upon Ca2+ binding. The exchanged EF-hands from TnC to CaM resulted in reduced hydrophobicity compared with wild-type CaM, as depicted by ANS fluorescence and binding affinity. Such a conclusion is consistent with general concepts about the inadequacy of hydrophobic exposure for chimeras. However, such ANS responses exhibited no correlation with the ability to interact with Orai1. ANS lifetime measurements indicated that there are two types of ANS molecules with rather distinct fluorescence lifetimes, each specifically corresponding to one lobe of CaM or chimeras. Thermodynamic studies indicated the interaction between CaM and a 24-residue peptide corresponding to the CaM-binding domain of Orail1 (Orai-CMBD) is a 1:2 CaM/Orai-CMBD binding, in which each peptide binding yields a similar enthalpy change (ΔH = − 5.02 ± 0.13 kcal/mol) and binding affinity (Ka = 8.92 ± 1.03 x 105 M−1). With the exchanged EF1 and EF2, the resulting chimeras noted as CaM(1TnC) and CaM(2TnC), displayed a two sequential binding mode with a one-order weaker binding affinity and lower ?H than that of CaM, while CaM(3TnC) and CaM(4TnC) had similar binding thermodynamics as CaM. Circular Dichroism studies suggested differences in binding most likely resulted from changes in chimera three-dimensional structure rather than secondary structure, as the extent of ?-helical content from apo-, Ca2+-, and Orai-CMBD-bound proteins remained similar. The dissociation rate constant for CaM/Orai-CMBD was determined to be 1.41 ± 0.08 s−1 by rapid kinetics. Stern-Volmer plots of Orai-CMBD Trp76, indicated that the residue is located in a very hydrophobic environment but becomes more solvent accessible when EF1 and EF2 were exchanged. Here, the model of 1:2 binding stoichiometry of CaM/Orai-CMBD established in solution supports the unique, open binding mode suggested by already published structural studies.

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Gueder, Nahla. "sp²-Iminosugar-glucosidases inhibitor 1-C-octyl-2-oxa-3-oxocastanospermine - induced antiproliferative, apoptotic and necrotic effects in breast cancer cells via targeting GRP78, Stim1 and Orai1." Thesis, Amiens, 2018. http://www.theses.fr/2018AMIE0033/document.

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L'altération de glycosylation est l'une des caractéristiques du cancer du sein. Ainsi le défaut de glycosylation affecte différentes protéines glycosylées responsables des différents processus cancéreux. Les canaux SOC (Store operated channels) constituent la voie majeure de l'entrée du calcium dans les cellules et sont impliqués dans la prolifération, la migration et la survie des cellules cancéreuses du sein. CO-OCS est un nouvel inhibiteur de la glycosylation avec plus de sélectivité vis-à-vis des α-glucosidases, et montre des activités anticancéreuses des cellules cancéreuses du sein, sans affecter les cellules mammaires normales. L'objectif de ma thèse est d'étudier les mécanismes moléculaires par lesquels CO-OCS induit ses effets anti-tumoraux. CO-OCS inhibe la migration des cellules cancéreuses à fort potentiel métastatique. Cet effet anti-migratoire est dû à une réduction de l'expression de la β1-intégrine, de Stim1, et de l'activation des voies de signalisation FAK et ERK1/2 par CO-OCS. Dans les cellules cancéreuses peu invasives, CO-OCS diminue la prolifération et augmente la mortalité de ces cellules en affectant l'expression de 3 protéines : Stim1 et Orai1 : protéines N-glycosylées au niveau du réticulum endoplasmique (RE), et GRP78, protéine de stress du RE. Ainsi en supprimant complétement l'expression de Stim1, CO-OCS réduit la prolifération en accumulant les cellules dans les phases G1 et G2/M du cycle cellulaire. Alors que la réduction de l'expression de GRP78 et d'Orai1 par le CO-OCS augmente respectivement l'apoptose et la nécrose. Par ailleurs, l'invalidation de Stim1 atténue l'effet apoptotique induit par CO-OCS. CO-OCS réduit aussi le contenu calcique du RE. Cette réduction du calcium réticulaire est due à une fuite de calcium par le Translocon. En effet, l'Anisomycine, inhibiteur du Translocon, restore de contenu calcique réticulaire et antagonise l'apoptose induite par le CO-OCS. En conclusion, CO-OCS induit une accumulation de protéines mal-repliées dans le RE induisant ainsi un stress réticulaire. Trois cibles du CO-OCS ont été identifiées : l'expression de Stim1 favorise la prolifération tandis que celle d'Orai1 et de GRP78 protègent respectivement les cellules de l'apoptose et de la nécrose induites par CO-OCS. De plus, en diminuant l'expression de GRP78, CO-OCS induit une fuite du calcium du RE par le Translocon
Alteration in glycosylation pattern is one of the hallmarks of breast cancer. The levels and the abnormal expressions of glycan were found in breast cancer patients. Glycosylation defect can affect different glycosylated proteins which are implicated in cancerogenesis. Changes in intracellular Ca2+ levels can regulate different cellular processes. SOC channels are implicated in breast cancer proliferation, migration and survival. CO-OCS is a new glycosylation inhibitor with more selectivity toward theα- glucosidases exhibited anti-cancer activities in breast cancer cells without affecting the normal mammary cells. The objective of my thesis is investigating the related molecular mechanisms by which CO-OCS induced its anti-tumour effects.CO-OCS impaired breast cancer migration through decrease β1-integrin expression and the activation of FAK and ERK1/2 signalling pathways. CO-OCS also induced anti-migratory effect via Stim1 protein expression down-regulation leading to inhibition of SOCE. Additionally, CO-OCS affected the expression of both Orai1 and Stim1 proteins leading to anti-proliferative effects and cell cycle arrest in G1 and G2/M phase respectively. Moreover, CO-OCS affected the expression of Stim1 at the protein level without affecting its transcript level. GRP78 implicated in CO-OCS apoptotic death. The expression of Stim1 regulated the apoptosis induced by CO-OCS via modulating GRP78 expression. Orai1 down-regulation promoted CO-OCS necrotic effect. CO-OCS induced ER- calcium depletion due to increase in ER calcium leak via the Translocon; Anisomycin (Translocon inhibitor) decreased the apoptosis induced by CO-OCS. In conclusion, these results show that in breast cancer, by targeting Stim1, Orai1 and GRP78, CO-OCS reduced cell proliferation and induced apoptosis and necrosis cell death. Stim1 favours CO-OCS apoptotic effect while Orai1 protected from necrosis induced by CO-OCS. The inhibition of Translocon decreased CO-OCS apoptotic cell death via restoring the ER calcium homeostasis
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Bartoli, Fiona. "Le canal calcique Orai1 : nouvel acteur impliqué dans la physiopathologie cardiaque." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS027.

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Alors que l’entrée SOC (store-operated Ca2+ entry) portée par les canaux calciques TRPCs (transient receptor potential canonical) et Orai1 est essentielle dans les cellules non-excitables, son rôle physiologique dans les cardiomyocytes adultes reste à élucider. Néanmoins, il est largement admis qu’une entrée SOC exacerbée dépendante des canaux TRPCs et de la protéine régulatrice STIM1 participe à la pathogenèse de l’hypertrophie et de l’insuffisance cardiaque (IC) par induction de voies pro-hypertrophiques telles que la CaMKII (Ca2+/calmoduline-dépendante kinase II ) et la calcineurine (CaN)/NFAT (Nuclear factor of activated T-cells). Au contraire, une inhibition fonctionnelle ou une extinction génique des canaux TRPCs et de la protéine STIM1 serait cardioprotectrice contre le stress hypertrophique. Cependant, le rôle physiopathologique des canaux calciques Orai1 dans le cœur reste, à ce jour, méconnu et débattu puisque son extinction in vitro présente un effet bénéfique contre l’hypertrophie des cardiomyocytes alors que son extinction in vivo présente des effets délétères avec le développement d’une cardiomyopathie dilatée. De plus amples investigations quant au rôle d’Orai1 dans la physiopathologie cardiaque apparaissent donc primordiales. De ce fait, les objectifs de ma thèse sont d’explorer le rôle de la signalisation calcique dépendante d’Orai1 dans le cœur dans des conditions physiologiques et pathologiques grâce à un modèle de souris transgéniques exprimant un mutant non fonctionnel d’Orai1, spécifiquement dans le cœur (dn-Orai1R91W/tTa) et un inhibiteur pharmacologique sélectif, le JPIII. Tout d’abord, nous montrons que les souris dn-Orai1R91W/tTa présentent une fonction cardiaque normale et une homéostasie calcique impliquée dans le couplage excitation-contraction conservée suggérant qu’Orai1 n’a pas de rôle majeur dans le coeur adulte en condition physiologique. Cependant, nous avons démontré une augmentation de l’expression et de l’activité d’Orai1 dans un modèle murin d’hypertrophie cardiaque induite par surcharge de pression, qui serait délétère pour la fonction ventriculaire. Au contraire, l’inhibition fonctionnelle d’Orai1 par manipulation génétique ou par l’outil pharmacologique (JPIII) semble protéger le coeur des dysfonctions ventriculaires au cours de l’hypertrophie. Cet effet bénéfique passerait par une restauration de l’homéostasie calcique et notamment par un maintien de l’expression de la pompe ATPase SERCA2a. Nous avons également mis en évidence que la voie de l’aldostérone/récepteurs aux minéralocorticoïdes modulait l’expression des canaux TRPC1, -C4, -C5 et notamment Orai1 via la protéine SGK1 (Serum and Glucocorticoid-regulated Kinase 1) dans les cardiomyocytes ventriculaires de rat nouveaux-nés. L’activation de cette voie de signalisation pourrait être à l’origine de la surexpression des canaux TRPCs/Orai1 retrouvée au cours de l’hypertrophie cardiaque. Ces travaux décrivent donc Orai1 comme une cible thérapeutique potentielle dans le traitement de l’hypertrophie cardiaque et de l’IC
While the SOCE (store-operated Ca2+ entry), carried by TRPCs (transient receptor potential canonical) and Orai1 channels, is essential in non-excitable cells, its physiological role in adult cardiomyocytes remains elusive. Nevertheless, it is well established that exacerbated TRPCs/STIM1-dependent Ca2+ entry participates in the pathogenesis of hypertrophy and heart failure (HF) via the induction of pro-hypertrophic signaling pathways, such as CaMKII (Ca2+/calmodulin-kinase II) and calcineurin (CaN)/ NFAT (nuclear factor of activated T-cells). By contrast, functional inhibition or gene silencing of TRPCs and STIM1 is cardioprotective against hypertrophic insults. As for Orai1 Ca2+ channels, their pathophysiological roles in the heart remain unknown and under debate, since in vitro Orai1 silencing has a beneficial effect against cardiomyocyte hypertrophy, whereas in vivo silencing has deleterious effects with the development of dilated cardiomyopathy. Further investigations are necessary to determine the pathophysiological role of Orai1 in the heart. My thesis objectives are to explore the role of Orai1-dependent Ca2+ signaling in the heart under physiological and pathological conditions using a transgenic mouse model expressing a non functional mutant of Orai1, specifically in the heart (dn-Orai1R91W/tTa) and a selective pharmacological inhibitor, JPIII. First, we showed that dn-Orai1R91W/tTa mice have normal cardiac function and conserved Ca2+ homeostasis involved in the excitation-contraction coupling suggesting that Orai1 is not instrumental in regulating cardiac function under physiological conditions. However, we demonstrated an increased Orai1 expression and activity in a mouse model of cardiac hypertrophy induced by pressure overload, which is a maladaptive alteration involved in pathological ventricular dysfunction. By contrast, functional inhibition of Orai1 by genetic manipulation or by the pharmacological tool (JPIII) protects the heart from ventricular dysfunction after pressure overload-induced cardiac hypertrophy. This beneficial effect is related to a restoration of Ca2+ homeostasis and more specifically, is due to preserved ATPase SERCA2a pump expression. We also showed that the aldosterone/mineralocorticoid receptor signaling pathway modulates the expression of TRPC1, -C4, -C5 channels and also the Orai1 channels expression via the SGK1 (Serum and Glucocorticoid-regulated Kinase 1) protein, in neonatal rat ventricular cardiomyocytes. The activation of this signaling pathway could be the cause of the TRPCs/Orai1 channels overexpression found during cardiac hypertrophy. In conclusion, our studies highlighted that Orai1 Ca2+ channels could constitute potential therapeutic target in the treatment of cardiac hypertrophy and HF
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5

Lur, Gyorgy. "STIM1, Orai1 and store operated calcium entry in pancreatic acinar cells." Thesis, University of Liverpool, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.539501.

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6

Clarysse, Lucie. "Régulation du canal SK3 par l'AMPc et le calcium extracellulaire dans les cellules cancéreuses du sein." Thesis, Tours, 2013. http://www.theses.fr/2013TOUR3312/document.

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Nous avons montré un rôle d’un canal K+, le canal SK3, dans la migration des cellules cancéreuses de sein MDA-MB-435s et le développement de métastases ostéolytiques du cancer du sein. Lors de l’ostéolyse, la [Ca²+]ext augmente dans le microenvironnement osseux. Nous avons voulu déterminer si cette élévation de [Ca²+]ext, pouvait moduler l’expression et l’activité du canal SK3. Nous avons montré que l’augmentation de la [Ca²+]ext: i) favorise l’expression du canal SK3. Cet effet fait intervenir le récepteur au calcium (CaSR), qui en diminuant la [AMPc]int réduit l’activité de la PKA et lève ainsi son inhibition de la transcription du gène KCNN3 (codant pour SK3) ; ii) favorise la migration cellulaire dépendante du canal SK3, mécanisme impliquant également le CaSR ; iii) active le canal SK3 qui, par ailleurs, voit son activité réduite par l’élévation d’AMPc intracellulaire. De plus, l’augmentation d’AMPc délocalise un canal calcique partenaire de SK3, le canal Orai1, et diminue l’entrée constitutive de Ca²+ et la migration dépendantes du canal SK3. En conclusion, nos résultats montrent que l’expression et l’activité de SK3 sont régulées par l’AMPc et le Ca2+ extracellulaire. Ceci permet d’envisager une nouvelle stratégie thérapeutique ciblant l’AMPc pour le traitement des métastases osseuses du cancer du sein
We showed that a K+ channel, SK3 channel, is a mediator of MDA-MB-435s breast cancer cells migration and of osteolytic bone metastasis development of breast cancer. Since [Ca²+]out rises during osteolysis, in bone microenvironment, we study if this [Ca²+]out elevation could modulate SK3 expression and activity. We show that [Ca²+]out elevation: i) increases SK3 expression threw CaSR activation which, in turn, decreases [cAMP]int and PKA activation, leading to loss of its inhibitory effect on KCNN3 transcription; ii) increases SK3-dependent migration threw CaSR activation; iii) increases SK3 channel activity that is in addition, decreased by [cAMP]int elevation. Furthermore, cAMP elevation moves the Ca2+ channel Orai1 (SK3 partner) outside of lipid rafts and reduces the SK3 dependent-constitutive Ca²+ entry and cell migration. Our results show that both SK3 expression and activity are regulated by cAMP and extracellular Ca²+. These results underscore an innovative opportunity to use therapeutic approaches targeting cAMP for the treatment of breast cancer bone metastasis
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Noyer, Lucile. "Role of Orai1 in prostate cancer proliferation and cancer stem cell quiescence/activation transition." Thesis, Lille 1, 2019. http://www.theses.fr/2019LIL1S111.

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Le cancer de la prostate (CaP) est le cancer le plus fréquent et le troisième plus mortel chez l’homme en Europe. Les cellules souches cancéreuses (CSC) représentent une sous population de cellules cancéreuses possédant des propriétés de cellules souches qui les rendent résistantes aux thérapies et hautement tumorigènes. Les CSCs sont ainsi associées aux phénomènes de dormance tumorale, puis de rechute suite à leur réactivation. Les mécanismes régulant la transition dormance/prolifération constituent donc une question centrale dans la prise en charge du cancer. L’importance des protéines Orai dans le CaP a déjà été montrée dans de précédentes études, via leur implication dans les canaux de type SOC (store-operated calcium channel) et ARC (arachidonic acid-regulated channel). Cependant, le rôle du canal Orai1 dans la prolifération du CaP, ou son éventuelle implication dans la physiologie des CSC, restaient inconnus. Parallèlement, pour répondre aux limitations de son ciblage direct, nous avons cherché à identifier ses protéines partenaires. Nous nous sommes ainsi intéressés au récepteur Sigma 1 (S1R), une protéine chaperonne dont l’expression augmente dans le CaP, et qui possède de nombreux modulateurs pharmacologiques utilisés en clinique. Ce travail avait donc un double objectif : étudier le rôle d’Orai1 dans le CaP et les CSC prostatiques, et caractériser fonctionnellement le rôle du S1R en tant que nouveau partenaire du canal Orai1. Ces travaux ont tout d’abord permis de mettre en évidence l’importance d’Orai1 dans le contrôle de la transition entre la quiescence et la prolifération des CSCs prostatiques via la voie NFAT. De plus, ces résultats ont été confirmés dans les CSCs de mélanome, montrant que le rôle d’Orai1 serait généralisable au-delà du modèle prostatique. Nous avons également montré que le S1R interagit directement avec Orai1 et module positivement son activité, impactant ainsi la prolifération des cellules cancéreuses prostatiques. Enfin, nous avons mis en évidence la régulation de l’expression de ces protéines par les androgènes, ce qui est d’importance cruciale dans l’évolution du CaP. Nos résultats ont donc permis l’identification d’un acteur central du contrôle de la prolifération du CaP (Orai1), et la caractérisation d’une nouvelle protéine partenaire du canal Orai1 dans le CaP : le S1R. Ces travaux montrent que le S1R et Orai1 pourraient constituer de nouveaux marqueurs intéressants, ainsi que de potentielles nouvelles cibles thérapeutiques
Prostate cancer (PCa) is the most frequent and the third deadliest cancer in men in Europe. Cancer stem cells (CSC) are a rare subset of cancer cells possessing stem cell properties leading to a high resistance to therapy and an enhanced tumorigenicity. As a result, CSCs have been linked to tumor dormancy and relapse upon reactivation. Thus, the mechanisms regulating CSC dormancy/activation transition are of critical importance in PCa. Previous studies showed the importance of Orai proteins in PCa, through their roles in SOC (store-operated channel) and ARC (arachidonic acid-regulated calcium channel) channels. But the role of Orai1 in PCa proliferation and CSC physiology remained to be studied. Moreover, in order to bypass current targeting limitations for Orai1, we aimed to identify a partner protein able to regulate Orai1 in PCa. For this purpose, we focused on the Sigma 1 receptor (S1R), a chaperone protein capable of ion channel regulation. Interestingly, S1R expression is increased in PCa and this protein can bind many pharmacological compounds currently used for other clinical applications. This work thus aimed to first study the role of Orai1 in PCa and CSC physiology, and then characterize the role of S1R as a new regulator of Orai1 in PCa. Our results first show that Orai1 is a key regulator of CSC transition between quiescence and proliferation via the NFAT pathway. Moreover, this role is not limited to PCa, since these results were also confirmed in melanoma CSCs. We also show here that the S1R directly interacts with Orai1 and increases its activity, thus modulating PCa cell proliferation. Finally, we characterized the regulation of Orai1 and S1R expression by androgens, which is highly significant during PCa development. Our results therefore allowed the identification of a key regulator of PCa proliferation (Orai1), and propose an alternative method for its targeting via the identification of its partner protein (S1R). These results could lead to the development of new markers and innovative therapeutic strategies
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Giachini, Fernanda Regina Casagrande. "Contribuição da via STIM1/Orai1 para as diferenças relacionadas ao sexo na entrada de cálcio em miócitos vasculares durante a hipertensão arterial." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/42/42136/tde-28092010-170302/.

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Os distúrbios na regulação da concentração de cálcio (Ca2+) citoplasmático contribuem para a patogênese da hipertensão arterial. Evidências sugerem que as moléculas de interação estromal (STIM) atuam como sensores dos estoques intracelulares de Ca2+, enquanto as proteínas Orai representam as subunidades que formam os canais de Ca2+ ativados pela liberação de Ca2+ (CRAC). Neste estudo avaliamos a participação de STIM1/Orai1 na regulação das concentrações de Ca2+ citoplasmático e na ativação da contração vascular em aortas de ratos hipertensos. Nossos resultados sugerem que a ativação de STIM1/Orai1 pode representar um novo mecanismo que modula alterações vasculares nos níveis de Ca2+ intracelular na hipertensão arterial e que contribui para as diferenças sexuais de reatividade vascular em animais hipertensos.
Disturbance in the regulation of cytoplasmic calcium (Ca2+) concentration contributes to the pathogenesis of hypertension. Evidences suggest that the stromal interaction molecule (STIM) acts as a sensor of intracellular Ca2+ stores, whereas Orai proteins are the subunits that form CRAC channels. In this study, we evaluated the role of STIM1/Orai1 in the regulation of cytoplasmic Ca2+ concentrations and in the activation of contraction in aortas from hypertensive rats. We also studied how the differential activation of this pathway contributes to sex differences observed between hypertensive rats, as well as the protective effects of the female sex hormones in the vasculature. Our results suggest that activation of STIM1/Orai1 may represent a new mechanism that modulates intracellular Ca2+ concentration during hypertension and contributes to sex differences in the vascular reactivity of hypertensive animals.
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Zanotto, Camila Ziliotto. "Papel da O-glicosilação com N-acetil-glucosamina (O-GlcNAc) no influxo e recaptação de cálcio pelo retículo sarcoplasmático em aorta de ratos: análise funcional." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/17/17133/tde-09092013-133940/.

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A O-glicosilação com N-acetil-glucosamina (O-GlcNAc) é uma modificação pós-translacional altamente dinâmica que modula diversas vias de sinalização. O processo de O-GlcNAc é controlado por duas enzimas: a enzima OGT é responsável por catalisar a adição de N-acetil-glucosamina no grupo hidroxila dos resíduos de serina e treonina, enquanto a OGA catalisa a remoção de O-GlcNAc das proteínas modificadas. Proteínas com importante papel na função vascular são alvo de O-GlcNAc e o aumento da expressão de proteínas modificadas por O-GlcNAc promove aumento da reatividade vascular para estímulos contráteis. Um dos mecanismos de extrema importância no controle do tônus vascular está ligado à regulação da concentração de cálcio (Ca2+) intracelular, onde destacamos a participação do sistema STIM1/Orai1. As moléculas de interação estromal (STIM) atuam como sensores dos estoques intracelulares de Ca2+ e as proteínas Orai representam as subunidades que formam os canais de Ca2+ ativados pela liberação de Ca2+ (CRAC). Neste estudo investigamos a hipótese de que o aumento dos níveis vasculares de proteínas glicosiladas aumenta a resposta contrátil em aorta de ratos, por mecanismos relacionados ao controle da concentração intracelular de Ca2+.Em nossos experimentos, utilizamos aortas torácicas de ratos incubadas com PugNAc (inibidor seletivo da OGA, ), por 24h. Utilizando protocolo experimental que permite avaliar contrações induzidas pelo influxo de Ca2+ e liberação de Ca2+ intracelular, demonstramos que a incubação com PugNAc aumentou a resposta contrátil à PE bem como a contração durante o período de influxo de Ca2+, induzida pela reintrodução de solução fisiológica contendo Ca2+ (1,56 mM). O bloqueio dos canais CRAC com 2-APB (100 ) e gadolíneo (Gd3+, 100 ) diminuiu significativamente as contrações induzidas pelo influxo de Ca2+ em aortas incubadas com PugNAc. Além disso, estas aortas apresentaram aumento da expressão protéica de STIM1, o que resultaria em maior influxo de Ca2+. A contração induzida por cafeína (20 mM) e serotonina (10 ), a qual reflete a capacidade funcional do retículo sarcoplasmático (RS) em captar Ca2+, foi maior em aortas incubadas com PugNAc. O papel da Ca2+-ATPase (SERCA) foi avaliado com a utilização de tapsigargina, bloqueador da SERCA. O efeito da tapsigargina foi semelhante em artérias incubadas com PugNAc e veículo, apesar do aumento de expressão proteica da SERCA em aortas incubadas com PugNAc. Como a proteína cinase C (PKC) é ativada por aumentos de Ca2+ intracelular, determinamos se a atividade de proteínas alvo da PKC estavam aumentadas. A incubação com PugNAc aumentou a expressão das formas fosforiladas da CPI-17, MYPT-1 e MLC. Em conjunto, estes resultados sugerem que a ativação de STIM1/Orai1, aumento da liberação de Ca2+ intracelular e ativação da via de sinalização da PKC podem representar mecanismos que modulam as alterações vasculares em resposta ao aumento de proteínas glicosiladas por O-GlcNAc.
Glycosylation with O-linked -N-acetyl-glucosamine (O-GlcNAc) is a highly dynamic post-translational modification. The process of O-GlcNAc is controlled by two enzymes: the OGT enzyme catalyses the addition of N-acetyl-glucosamine to the hydroxyl group of serine and threonine residues of a target protein, while OGA catalyzes the cleavage of O-GlcNAc from post-translationally-modified proteins. Proteins with an important role in vascular function are targets of O-GlcNAc and increased levels of proteins modified by O-GlcNAc increase vascular reactivity to contractile stimuli. The regulation of intracellular calcium (Ca2+) concentration, including the activation of STIM1/Orai1, is key in the control of vascular tone. The stromal interaction molecules (STIM) act as sensors of intracellular Ca2+ stores whereas the Orai proteins represent subunits of the Ca2+ release-activated Ca2+ channels (CRAC). We hypothesized that increased levels of vascular O-GlcNAc proteins augment vascular contractile responses by altering mechanisms that regulate the intracellular Ca2+. Rat thoracic aortas were incubated with PugNAc (OGA selective inhibitor, ) for 24h. Using an experimental protocol that evaluates contractions induced by Ca2+ influx and release, we demonstrated that incubation with PugNAc increases contractile responses to phenylephrine (PE) as well as the contraction induced by Ca2+ influx, after depletion of intracellular Ca2+ stores. The CRAC channel blockers, 2-APB (100 ) and gadolinium (Gd3+, 100 ), significantly reduced the contractions induced by Ca2+ influx in aortas incubated with PugNAc. Furthermore, these aortas showed increased STIM1 protein expression, which could result in increased influx of Ca2+ and, in turn, increase vascular contraction. The contraction induced by the release of intracellular Ca2+ stores, stimulated by caffeine (20 mM) and serotonin (10 ), was increased in aortas incubated with PugNAc. The Ca2+-ATPase (SERCA) inhibitor thapsigargin produced similar effects in arteries incubated with PugNAc or vehicle, despite the increased SERCA protein expression in aortas incubated with PugNAc. Since PKC is activated by increases in intracellular Ca2+ and arteries incubated with PugNAc show activation of PKC, we determined whether the activity of proteins that are targets of PKC was increased in PugNAc-treated aortas. Incubation with PugNAc increased the expression of phosphorylated forms of CPI-17, MYPT-1 and MLC. Together, these results suggest that activation of STIM1/Orai1, increased release of intracellular Ca2+ and PKC activation may represent mechanisms that modulate vascular responses upon increased O-GlcNAc proteins.
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10

Cabanas, Hélène. "Rôle de la signalisation calcique dans la leucémie myéloïde chronique." Thesis, Poitiers, 2016. http://www.theses.fr/2016POIT2302/document.

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La Leucémie Myéloïde Chronique (LMC) est une maladie clonale caractérisée par la présence du chromosome Philadelphie codant pour Bcr-Abl, une tyrosine kinase constitutivement active responsable de la leucémogenèse. Bien que très efficaces, les inhibiteurs de tyrosine kinase (ITKs) restent cependant inactifs sur les cellules souches leucémiques. Ce travail de thèse montre que la signalisation calcique, connue pour réguler de nombreux processus dans les cellules saines et cancéreuses, est importante dans la signalisation cellulaire au décours de la LMC. Le rôle des entrées calciques dépendantes des stocks (SOCEs) médiées par STIM1 (STromal Interaction Molecule 1) et les canaux Orai1 et TRPC1 ainsi que des entrées calciques induites par la thrombine a été étudié dans la leucémogenèse. Nous avons observé une diminution de ces entrées dans les cellules exprimant Bcr-Abl pouvant être expliquée par le changement de stœchiométrie Orai1/STIM1. Ceci entraîne la diminution de l'activation de NFAT (Nuclear Factor of Activated T-cells) ainsi que des conséquences sur la prolifération et la migration cellulaire mais pas sur l'apoptose. De plus, les SOCEs sont restaurées dans les cellules cancéreuses après traitement à l'Imatinib, le principal ITK. Nous proposons alors que l'expression de Bcr-Abl joue un rôle sur l'homéostasie calcique en entraînant une dérégulation générale des fonctions cellulaires dans les cellules leucémiques notamment via la voie PKC (Protein Kinase C). Ainsi, ces résultats montrent une dérégulation des entrées calciques dans les cellules exprimant Bcr-Abl, suggérant que la signalisation calcique puisse être une cible thérapeutique en parallèle avec les ITKs
Chronic Myeloid Leukemia (CML) is a clonal disease characterized by the presence of the Philadelphia chromosome encoding for Bcr-Abl, a constitutively active tyrosine kinase responsible for leukemogenesis. Although Bcr-Abl tyrosine kinase inhibitors (TKIs) have revolutionized the therapy of Ph+ leukemia, the complete eradication of CML is limited by the emergence of resistance in hematopoietic stem cells. This thesis proposes that calcium (Ca2+) signaling pathways, known to govern a large number of functions in normal and cancer cells, may be important in CML cell signaling. Therefore, we studied the role of Store Operated-Calcium entry (SOCE) (i.e. STromal Interaction Molecule 1 (STIM1), Orai1 and TRPC1 channels) and thrombin induced Ca2+ entry in leukemogenesis. We found a decrease in both calcium entries in Bcr-Abl-expressing cells compared to normal cells. The reduced SOCE seems related to a change in stoichiometry of Orai1/STIM1. This leads to a reduction of the Nuclear Factor of Activated T-cells (NFAT) translocation and functional consequences on cell proliferation and migration but not on apoptosis. Moreover, we showed that SOCE is restored in malignant cells after treatment with Imatinib, the main TKI. We proposed that Bcr-Abl expression could impact on Ca2+ homeostasis enhancing a general disorganization of cell functions in leukemia cells notably via Protein Kinase C (PKC) pathway. Altogether this work shows a deregulation of Ca2+ entry in Bcr-Abl-expressing cells, suggesting that the Ca2+ signaling pathway could be a therapeutic target in parallel with TKIs
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Books on the topic "Orai1"

1

Arquivo Público do Distrito Federal (Distrito Federal, Brazil), ed. Depoimentos orais: Catálogo. 2nd ed. Brasília: Arquivo Público do Distrito Federal, 2008.

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Arquivo Público do Distrito Federal (Distrito Federal, Brazil), ed. Depoimentos orais: Catálogo. 2nd ed. Brasília: Arquivo Público do Distrito Federal, 2008.

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Kahakudo orai. Fukuoka-shi: Sogensha, 2004.

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1930-, Preti Dino, Rodrigues Angela C. S, and Projeto de Estudo da Norma Lingüística Urbana Culta de São Paulo., eds. Análise de textos orais. São Paulo, SP: FFLCH/USP, 1993.

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Arquivo Público do Distrito Federal (Distrito Federal, Brazil), ed. Catálogo de depoimentos orais. Brasília: O Arquivo, 1994.

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S, Rodrigues Angela C., Preti Dino 1930-, and Projeto de Estudo da Norma Lingüística Urbana Culta de São Paulo., eds. Análise de textos orais. 4th ed. São Paulo, SP, Brasil: Humanitas Publicações, FFLCH/USP, 1999.

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Rodrigues, Angela C. S., and Dino Preti. Análise de textos orais. 7th ed. São Paulo, SP, Brasil: Humanitas, 2010.

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1930-, Preti Dino, Rodrigues Angela C. S, and Projeto de Estudo da Norma Lingüística Urbana Culta de São Paulo., eds. Análise de textos orais. São Paulo, SP: FFLCH/USP, 1993.

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Orain ghaoil: Amhráin ghrá. Baile Átha Cliath: Coiscéim, 1990.

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Fred, Macaulay, ed. Dòmhnall Ruadh Chorùna: Orain is dain. Loch nam Madadh, Uibhist a Tuath: Comann Eachdraidh Uibhist a Tuath, 1995.

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Book chapters on the topic "Orai1"

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Yee, Christina. "Calcium Channel Defects (STIM1 and ORAI1)." In Encyclopedia of Medical Immunology, 86–91. New York, NY: Springer New York, 2020. http://dx.doi.org/10.1007/978-1-4614-8678-7_176.

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Yee, Christina. "Calcium Channel Defects (STIM1 and ORAI1)." In Encyclopedia of Medical Immunology, 1–6. New York, NY: Springer New York, 2019. http://dx.doi.org/10.1007/978-1-4614-9209-2_176-1.

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Derler, Isabella, Josef Madl, Gerhard Schütz, and Christoph Romanin. "Structure, Regulation and Biophysics of ICRAC, STIM/Orai1." In Advances in Experimental Medicine and Biology, 383–410. Dordrecht: Springer Netherlands, 2012. http://dx.doi.org/10.1007/978-94-007-2888-2_16.

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Woo, Jin Seok, Sonal Srikanth, and Yousang Gwack. "Modulation of Orai1 and STIM1 by Cellular Factors." In Calcium Entry Channels in Non-Excitable Cells, 73–92. Boca Raton : Taylor & Francis, 2017. | Series: Methods in signal transduction series: CRC Press, 2017. http://dx.doi.org/10.1201/9781315152592-4.

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Cheng, Kwong Tai, Hwei Ling Ong, Xibao Liu, and Indu S. Ambudkar. "Contribution of TRPC1 and Orai1 to Ca2+ Entry Activated by Store Depletion." In Transient Receptor Potential Channels, 435–49. Dordrecht: Springer Netherlands, 2010. http://dx.doi.org/10.1007/978-94-007-0265-3_24.

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Zhou, Yandong, Youjun Wang, and Donald L. Gill. "Assessing the Molecular Nature of the STIM1/Orai1 Coupling Interface Using FRET Approaches." In Calcium Entry Channels in Non-Excitable Cells, 127–44. Boca Raton : Taylor & Francis, 2017. | Series: Methods in signal transduction series: CRC Press, 2017. http://dx.doi.org/10.1201/9781315152592-7.

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Cioffi, Donna L., Christina Barry, and Troy Stevens. "Store-Operated Calcium Entry Channels in Pulmonary Endothelium: The Emerging Story of TRPCS and Orai1." In Advances in Experimental Medicine and Biology, 137–54. Totowa, NJ: Humana Press, 2009. http://dx.doi.org/10.1007/978-1-60761-500-2_9.

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Pacheco, Jonathan, A. Bohórquez-Hernández, Kevin M. Méndez-Acevedo, Alicia Sampieri, and Luis Vaca. "Roles of Cholesterol and PtdIns(4,5)P2 in the Regulation of STIM1–Orai1 Channel Function." In Advances in Experimental Medicine and Biology, 305–26. Cham: Springer International Publishing, 2023. http://dx.doi.org/10.1007/978-3-031-21547-6_11.

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Salido, Gines M., Isaac Jardín, and Juan A. Rosado. "The TRPC Ion Channels: Association with Orai1 and STIM1 Proteins and Participation in Capacitative and Non-capacitative Calcium Entry." In Transient Receptor Potential Channels, 413–33. Dordrecht: Springer Netherlands, 2010. http://dx.doi.org/10.1007/978-94-007-0265-3_23.

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Bartoli, Fiona, and Jessica Sabourin. "Cardiac Remodeling and Disease: Current Understanding of STIM1/Orai1-Mediated Store-Operated Ca2+ Entry in Cardiac Function and Pathology." In Store-Operated Ca²⁺ Entry (SOCE) Pathways, 523–34. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-57732-6_26.

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Conference papers on the topic "Orai1"

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Hubrack, Satanay, Ethel Adap, Stefan Feske, and Khaled Machaca. "Role Of Stim1 And Orai1 In Mammalian Oocyte Activation." In Qatar Foundation Annual Research Conference Proceedings. Hamad bin Khalifa University Press (HBKU Press), 2014. http://dx.doi.org/10.5339/qfarc.2014.hbpp0176.

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Hubrack, Satanay Zuhair, Awab Ibrahim, and Khaled Machaca. "Study of the Effect of Calreticulin on Orai1 Function." In Qatar Foundation Annual Research Conference Proceedings. Hamad bin Khalifa University Press (HBKU Press), 2016. http://dx.doi.org/10.5339/qfarc.2016.hbpp1846.

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Ahmad, S., J. Wrennall, M. Sassano, and R. Tarran. "ELD607, a Novel Anti-Orai1 Peptide Reduces Pulmonary Inflammation." In American Thoracic Society 2021 International Conference, May 14-19, 2021 - San Diego, CA. American Thoracic Society, 2021. http://dx.doi.org/10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a1248.

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Masson, Bastien, Hélène Le Ribeuz, Jessica Sabourin, Emily Woodhouse, Richard Foster, Yann Ruchon, Mary Dutheil, et al. "Late Breaking Abstract - Involvement of Orai1 Ca2+ channel in the pathogenesis of pulmonary arterial hypertension. Orai1 as a new potential therapeutic target ?" In ERS International Congress 2021 abstracts. European Respiratory Society, 2021. http://dx.doi.org/10.1183/13993003.congress-2021.pa599.

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Pelzl, L., I. Sahu, D. Heinzmann, A. A. M. Bhuyan, T. a. Maghout, I. Marini, F. Rigoni, et al. "Phosphate-induced ORAI1 Expression and Store Operated Ca2+ Entry in Megakaryocytes." In 63rd Annual Meeting of the Society of Thrombosis and Haemostasis Research. Georg Thieme Verlag KG, 2019. http://dx.doi.org/10.1055/s-0039-1680097.

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Latour, Simon, Isabelle Mahouche, Floriane Cherrier, Jean-Philippe Merlio, Sandrine Poglio, and Laurence Bresson Bepoldin. "Abstract 1881: STIM1 and Orai1 control non-Hodgkin lymphoma cells migration." In Proceedings: AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7445.am2017-1881.

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Ahmad, S., M. Biggart, F. Sassano, A. Ghosh, and R. Tarran. "The Orai1 Antagonist, ELD607, Reduces Chronic Neutrophilic Inflammation in βENaC Mice." In American Thoracic Society 2024 International Conference, May 17-22, 2024 - San Diego, CA. American Thoracic Society, 2024. http://dx.doi.org/10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a6682.

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Dib, Maya, Rawad Hodeify, and Khaled Machaca. "Identification Of Proteins Involved In Orai1 Trafficking By Mass Spectrometry-based Approach." In Qatar Foundation Annual Research Conference Proceedings. Hamad bin Khalifa University Press (HBKU Press), 2014. http://dx.doi.org/10.5339/qfarc.2014.hbpp048.

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Tarran, R., S. Ahmad, J. Wrennal, E. N. Worthington, and M. F. Sassano. "Local Orai1 Inhibition Reduces Pulmonary Inflammation in House Dust Mite-Exposed Mice." In American Thoracic Society 2020 International Conference, May 15-20, 2020 - Philadelphia, PA. American Thoracic Society, 2020. http://dx.doi.org/10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a7422.

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Yang, Shengyu, Jianwei Sun, and Huifang He. "Abstract 4317: Stim1 and Orai1 are critical regulators of melanoma invasion and anoikis." In Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL. American Association for Cancer Research, 2012. http://dx.doi.org/10.1158/1538-7445.am2012-4317.

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Reports on the topic "Orai1"

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Huang, Xin-Yun. Orai1 as New Therapeutic Target for Inhibiting Breast Tumor Metastasis. Fort Belvoir, VA: Defense Technical Information Center, September 2009. http://dx.doi.org/10.21236/ada518249.

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Canto, Patricia, ed. Euskal Autonomia Erkidegoko Lehiakortasunari buruzko 2021eko Txostena. Ongizatea helburu duen lehiakortasuna eraikitzea. Universidad de Deusto, 2021. http://dx.doi.org/10.18543/zemz8571.

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Txosten honek, EAEko lehiakortasunaren azterketan etapa berri bat hastendu. 1. kapituluan, gure lurraldearen lehiakortasun ibilbidea aztertu dugu, orain dela 40 urte abian jarri zen estrategiak azken hamarkadan izan dituen ezaugarriei erreparatuta bereziki. Estrategia horrekin jarraitzeak gaur egun ekartzen dizkigun erronkak ere identifikatu ditugu. Estrategiaren hurrengo etapa bideratzeko, erronka horietatik abiatu gara eta, 2. kapituluan, lurralde lehiakortasuna bultzatzeko esparru berri bat proposatu dugu, tokian bertan eta nazioartean egindako gogoeta, alderatze eta esperimentazio prozesu baten ondoren. 3. kapituluan, EAEko lehiakortasunaren eta ongizatearen lehenengo diagnostikoa aurkeztu dugu, esparru berriaren ardatz nagusietan oinarrituta. Esparru berrian ongizatea helburu duen lehiakortasunerako sei palankak identifikatu ostean, 4. kapituluan, palanka horien dimentsioetako batzuen esplorazio analisia egin dugu. Bukatzeko, azken kapituluan diagnostikoaren ondorio nagusiak bildu ditugu eta esparruaren bilakaera bideratzeko pausoen inguruan gogoeta egin dugu, esparrua Euskal Autonomia Erkidegoko ongizaterako lehiakortasuna etengabe hobetzen lagunduko duen itsasargia izan dadin.
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Schmidt-Sane, Megan, and Tabitha Hrynick. Guia de Orientação Sobre o Envolvimento da Comunidade na Resposta a Surtos de Cólera na Região da Africa Oriental e Austral. Institute of Development Studies, May 2023. http://dx.doi.org/10.19088/sshap.2023.009.

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Os surtos de cólera têm vindo a aumentar na Região da África Oriental e Austral (AOA) desde Janeiro de 2023, com uma transmissão generalizada e alargada no Malawi e em Moçambique e surtos registados na Tanzânia, na África do Sul, no Zimbabué, no Burundi e na Zâmbia.1 Existe o risco de uma maior propagação causada pelos efeitos do ciclone Freddy, que atingiu Madagáscar, o Malawi e Moçambique em Março de 2023. Continuam a registar-se surtos na Somália, na Etiópia, no Quénia e no Sudão do Sul, onde os países estão a atravessar uma situação de seca após sucessivas estações chuvosas deficitárias.1 O contexto de resposta na AOA é complexo. Isto deve-se à escassez de recursos de saúde pública, incluindo a insuficiência de vacinas orais contra a cólera, e às múltiplas emergências de saúde pública e humanitárias simultâneas, incluindo a reemergência do poliovírus selvagem. O envolvimento da comunidade nas respostas ao surto de cólera é essencial, especialmente enquanto o impacto da COVID-19 ainda se faz presente na região, sobretudo no que tange à confiança na saúde pública e nos esforços de vacinação.2,3 O objectivo do presente guia de orientação é apoiar os Ministérios da Saúde, a UNICEF e outros parceiros de resposta na concepção e implementação de um envolvimento comunitário eficaz, centrado na comunidade e baseado em dados, para a resposta ao surto de cólera. Este guia de orientação foi redigido em abril de 2023 por Megan Schmidt-Sane e Tabitha Hrynick (IDS), com a colaboração de Stellar Murumba (Internews), Ngonidzashe Macdonald Nyambawaro (FICV), Eva Niederberger (Anthrologica), Santiago Ripoll (IDS), Nadine Beckmann (LSHTM), Mariana Palavra (UNICEF) e Rachel James (UNICEF). Este guia de orientação tem por base o trabalho anterior sobre a cólera da Social Science in Humanitarian Action Platform (SSHAP).
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Nazioen Lehiatzeko Abantaila: Esperientzia arrakastatsua, Euskal Autonomia Erkidegoaren ekonomia eta gizarte garapenerako estrategia eraldatzailea bideratzekona. Universidad de Deusto, 2015. http://dx.doi.org/10.18543/pdmc8484.

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Ekonomia berriak eta ongizate gizarteek zergatik gomendatuko lukete geraleku berri bat jartzea lehiakortasunerako bidaia luzean, duela 25 urte argitaratu zen "nazioen lehiatzeko abantailaren" ildotik? Orain dela hogeita bost urte baino gehixeago, Euskal Autonomia Erkidegoak garapenerako bere estrategia eraikitzearen aldeko apustua egin zuen eta bere etorkizuna diseinatzeko erronkarekin konpromisoa hartu. Euskal Autonomia Erkidegoak ahalik eta autogobernu mailarik handiena eskuratu nahi zuen, Estaturik gabeko nazio izanik, diktadura luzetik atera ostean. Hain zuzen ere, diktadurak Espainiako ekonomia autarkikoa izatea eragin zuen, mendebaldeko demokrazietatik guztiz isolatua. Horrek guztiz mugatzen zuen euskal erakundeek beren etorkizuna eraikitzeko izan zezaketen ahalmena eta erantzukizuna, baita gizarteari ongizate maila handiagoa lortzen laguntzeko erabil zitzaketen tresnak ere. Garai hartan, euskal ekonomiak historiako krisi ekonomiko, politiko eta sozial handienetako bat bizi zuen: indarkeriak gogor jotzen zuen gizartea, langabezia % 25etik gorakoa zen, BPG jaisten ari zen, eta industria sektore gakoak –altzairuaren nagusitasunean eta industria metal-mekanikoaren inguruan egituratuak– erortzen ari ziren, domino fitxen moduan. Garai bertsuan, Europako sei herrialde Ekonomia Elkartea osatzen hasiak ziren, baina gu periferian geunden, guztiz baztertuta, Londres-Milan etorkizuneko ardatz izango zen "banana urdinetik" urrun. Administrazio berria eraikitzen hasi berriak ginen, inongo esperientziarik gabe, baina ilusio handiz; eta enpresa mundua garai berrietara moldatzen eta sindikatuekin bizitzen ikasten ari zen, diktadura zaharrak haiek ezkutuan utzi baitzituen. Erronka konplexu baina zirraragarri horren aurrean, apustu hori lantzeko pribilegioa izan genuenok, lehenengo, munduko ekonomiaren egoera azalduko zuten gako nagusiak eta aldaketaren joera nagusiak interpretatzeari ekin genion (gure analisiak eginez eta gure asmoak eta ametsak egi bihurtu nahian), eta euskal ekonomian izan zezaketen eragina aztertzen hasi ginen (“Munduko ekonomiak erakusten diguna"). Eta, abiapuntu horretatik aurrera, “Geure ekonomia eta geure herrialdea modernizatzeko eta nazioartekotzeko estrategia” deitutakoa definitzen hasi ginen. Zentzua eman nahi genion jokalari berriengandik (Estatuak, hiri-eskualdeak, lurraldeak…) espero zitekeen rolari; izan ere, rol horietan gure herrialde txikia –hirieskualdearen ezaugarriak zituena, nazioz azpiko eremua izanik, Pirinioen bi aldeetara egituratu gabeko eremuan–, beste batzuekin batera, protagonista izan zitekeen eta, horrela, gizarteari etorkizun oparoa eskaini. Arrakastako estrategia aurrera eramateko esparru eta tresna egokiak ere behar genituen. Paradigma berriek sortuko zituzten beharren eta garai hartako gure esparru politiko-ekonomikoak eskaintzen zizkigun tresnen (edukiak, gaitasunak, garapen potentzialak) arteko aldea identifikatu genuen, eta azterketa horri herrialdearen estrategia erantsi genion, geurea, arreta berezia eskaintzen ziena gure gizarteak, ongizate eta garapen maila jakin bat erdiesteko, behar zituen ekimenei eta faktore edo bektore kritikoei. Testuinguru horretan, Eusko Jaurlaritza Michael E. Porterrengana hurbildu zen, garai hartako bere ideia eta kontzeptuetara, eta lankidetza prozesu bati ekin genion (gaur egun oraindik ere indarrean dagoena). Horrela, "Euskal Autonomia Erkidegoko lehiatzeko abantaila” baino gehiago eraiki genuen, “lehiakortasunerako eta oparotasunerako bidaia" zirraragarri eta amaitu gabean. Euskal Autonomia Erkidegoak pribilegio bat du orduz geroztik: Porterrek proposatutako kontzeptuak, ikuspegi estrategikotik eta osotasunean, aplikatu zituen lehenengo nazioa izatea. Hain zuzen ere, kontzeptu horiek, urte batzuk geroago, "Nazioen Lehiatzeko Estrategia” liburu ospetsuan argitaratu zituen, orain dela hogeita bost urte. Lan horrek, mundu osoan zehar, politika eta estrategia zenbatezinak diseinatzea ekarri du, jarraitzaileak ugaritzea, prestatzaileak prestatzea, ikertzaile eta akademiko berri asko eta asko sortzea, policy maker berriak, lehiakortasunerako tresna berriak, eta oparotasun maila ikusgarriak planeta osoan zehar. Orduz geroztik, gure proiektu berezi, bizi eta aldakor honetan elkarrekin lan egin dugu, erronka berriei eta ekonomiaren eta gizartearen eskari berriei erantzunez, eta Herrialde mailako estrategia bat eraikiz eta gauzatuz. Horrek guztiak ekarri du gure emaitzak inguruko ekonomienak baino hobeak izatea. Michael E. Porterrek Lehiatzeko Abantailan proposatzen duen kontzeptuaren osagarri berriak ere (Lehiakortasunaz gainera, Shared Value Initiative eta Gizarte Aurrerapena) kontuan hartzen dituen esparru kontzeptuala aurrean izanik eta egunez egun ikasitako ekarpenekin, geure bokazio, izaera, borondate eta konpromisoarekin guztiz lerrokatuta. Prozesu amaigabea, pertsonak abiapuntu eta helmuga hartzen dituen estrategia eraikitzeko apustu zaharraren eredutik eta ulertzeko modutik hasi zena.
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