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https://www.readbyqxmd.com/read/29337674/a-study-on-blocking-store-operated-ca2-entry-in-pulmonary-arterial-smooth-muscle-cells-with-xyloketals-from-marine-fungi
#1
Jie-Bin Zhou, Ying-Ying Sun, Ying-Lin Zheng, Chu-Qin Yu, Hua-Qing Lin, Ji-Yan Pang
In this study, the effect of four xyloketals 1-4 on store-operated calcium entry (SOCE) was investigated in primary distal pulmonary arterial smooth muscle cells (PASMCs) isolated from mice. The results showed that xyloketal A (1), an unusual ketal with C-3 symmetry, exhibited strong SOCE blocking activity. Secretion of interleukin-8 (IL-8) was also inhibited by xyloketal A. The parallel artificial membrane permeability assay (PAMPA) of 1-4 suggested that these xyloketals penetrated easily through the cell membrane...
December 20, 2017: Acta Pharmaceutica
https://www.readbyqxmd.com/read/29326165/phosphorylation-mediated-structural-changes-within-the-soar-domain-of-stim1-enable-specific-activation-of-distinct-orai-channels
#2
Jill L Thompson, Yue Zhao, Peter B Stathopulos, Alan Grossfield, Trevor J Shuttleworth
The low-conductance, highly calciumselective channels formed by the Orai proteins are known to take two major forms, namely the storeoperated CRAC channels, and store-independent, arachidonic acid-activated ARC channels. Both are activated by STIM1, but whereas CRAC channels are activated by the stromal-interacting STIM1 located in the endoplasmic reticulum membrane, ARC channels are activated by the minor pool of STIM1 located in the plasma membrane. Critically, maximally activated CRAC channel currents and ARC channel currents are completely additive within the same cell, demonstrating that these two channels are entirely distinct entities...
January 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29323264/orai3-calcium-channel-and-resistance-to-chemotherapy-in-breast-cancer-cells-the-p53-connection
#3
Jessy Hasna, Frédéric Hague, Lise Rodat-Despoix, Dirk Geerts, Catherine Leroy, David Tulasne, Halima Ouadid-Ahidouch, Philippe Kischel
Orai proteins are highly selective calcium channels playing an important role in calcium entry. Orai3 channels are overexpressed in breast cancer (BC) tissues, and involved in their proliferation, cell cycle progression and survival. Herein, we sought to address the involvement of Orai3 in resistance to chemotherapeutic drugs. Using high-throughput approaches, we investigated major changes induced by Orai3 overexpression, including downstream signaling mechanisms involved in BC chemotherapy resistance. Resistance was dependent on external calcium presence and thus Orai3 functionality...
January 11, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29298434/coiled-coil-formation-conveys-a-stim1-signal-from-er-lumen-to-cytoplasm
#4
Nupura Hirve, Vangipurapu Rajanikanth, Patrick G Hogan, Aparna Gudlur
STIM1 and STIM2 are endoplasmic reticulum (ER) membrane proteins that sense decreases in ER-luminal free Ca2+ and, through a conformational change in the STIM cytoplasmic domain, control gating of the plasma membrane Ca2+ channel ORAI1. To determine how STIM1 conveys a signal from the ER lumen to the cytoplasm, we studied the Ca2+-dependent conformational change of engineered STIM1 proteins in isolated ER membranes and, in parallel, physiological activation of these proteins in cells. We find that conserved "sentinel" features of the CC1 region help to prevent activation while Ca2+ is bound to STIM ER-luminal domains...
January 2, 2018: Cell Reports
https://www.readbyqxmd.com/read/29237734/authentic-crac-channel-activity-requires-stim1-and-the-conserved-portion-of-the-orai-n-terminus
#5
Isabella Derler, Carmen Butorac, Adela Krizova, Michael Stadlbauer, Martin Muik, Marc Fahrner, Irene Frischauf, Christoph Romanin
Calcium (Ca2+) is an essential second messenger required for diverse signaling processes in immune cells. Ca2+ release-activated Ca2+ (CRAC) channels represent one main Ca2+ entry pathway into the cell. They are fully reconstituted via two proteins, the stromal interaction molecule 1 (STIM1), a Ca2+ sensor in the endoplasmic reticulum and the Ca2+ ion channel Orai in the plasma membrane. After Ca2+ store depletion, STIM1 and Orai couple to each other allowing Ca2+ influx. CRAC-/STIM1-mediated Orai channel currents display characteristic hallmarks such as high Ca2+ selectivity, an increase in current density when switching from a Ca2+-containing solution to a divalent-free Na+ one and fast Ca2+ dependent inactivation...
December 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29237733/communication-between-n-terminus-and-loop2-tunes-orai-activation
#6
Marc Fahrner, Saurabh K Pandey, Martin Muik, Lukas Traxler, Carmen Butorac, Michael Stadlbauer, Vasilina Zayats, Adéla Krizova, Peter Plenk, Irene Frischauf, Rainer Schindl, Hermann J Gruber, Peter Hinterdorfer, Rüdiger Ettrich, Christoph Romanin, Isabella Derler
Ca2+ release-activated Ca2+ (CRAC) channels constitute the major Ca2+ entry pathway into the cell. They are fully reconstituted via intermembrane coupling of the Ca2+ selective Orai channel and the Ca2+ sensing protein STIM1. In addition to the Orai C-terminus, the main coupling site for STIM1, the Orai N-terminus is indispensable for Orai channel gating. Although the extended transmembrane Orai N-terminal (ETON) region (Orai1: aa73-91; Orai3: aa48-65) is fully conserved in the Orai1 and Orai3 isoforms, Orai3 tolerates larger N-terminal truncations than Orai1 in retaining store-operated activation...
December 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29217255/forms-and-functions-of-store-operated-calcium-entry-mediators-stim-and-orai
#7
REVIEW
James W Putney
Calcium signals arise by multiple mechanisms, including mechanisms of release of intracellular stored Ca2+, and the influx of Ca2+ through channels in the plasma membrane. One mechanism that links these two sources of Ca2+ is store-operated Ca2+ entry, the most commonly encountered version of which involves the extensively studied calcium-release-activated Ca2+ (CRAC) channel. The minimal and essential molecular components of the CRAC channel are the STIM proteins that function as Ca2+ sensors in the endoplasmic reticulum, and the Orai proteins that comprise the pore forming subunits of the CRAC channel...
November 22, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29210464/ca2-and-lipid-signals-hold-hands-at-er-plasma-membrane-contact-sites
#8
Tamas Balla
Discovery of the STIM1 and Orai proteins as the principal components of store-operated Ca2+ entry (SOCE) has drawn attention to contact sites between the ER and the plasma membrane (PM). Such contacts between adjacent membranes of different cellular organelles, primarily between the mitochondria and the ER, had already been known as the sites where Ca2+ released from the ER can be efficiently channeled to the mitochondria and also where phosphatidylserine synthesis and transfer takes place. Recent studies have identified contact sites between virtually every organelle and the ER and the functional importance of these small specialized membrane domains is increasingly recognized...
December 6, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29203863/orai-channels-are-critical-for-receptor-mediated-endocytosis-of-albumin
#9
Bo Zeng, Gui-Lan Chen, Eliana Garcia-Vaz, Sunil Bhandari, Nikoleta Daskoulidou, Lisa M Berglund, Hongni Jiang, Thomas Hallett, Lu-Ping Zhou, Li Huang, Zi-Hao Xu, Viji Nair, Robert G Nelson, Wenjun Ju, Matthias Kretzler, Stephen L Atkin, Maria F Gomez, Shang-Zhong Xu
Impaired albumin reabsorption by proximal tubular epithelial cells (PTECs) has been highlighted in diabetic nephropathy (DN), but little is known about the underlying molecular mechanisms. Here we find that ORAI1-3, are preferentially expressed in PTECs and downregulated in patients with DN. Hyperglycemia or blockade of insulin signaling reduces the expression of ORAI1-3. Inhibition of ORAI channels by BTP2 and diethylstilbestrol or silencing of ORAI expression impairs albumin uptake. Transgenic mice expressing a dominant-negative Orai1 mutant (E108Q) increases albuminuria, and in vivo injection of BTP2 exacerbates albuminuria in streptozotocin-induced and Akita diabetic mice...
December 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/29188077/orai1-2-3-and-stim1-promote-store-operated-calcium-entry-in-pulmonary-arterial-smooth-muscle-cells
#10
Jian Wang, Chuyi Xu, Qiuyu Zheng, Kai Yang, Ning Lai, Tao Wang, Haiyang Tang, Wenju Lu
Previous studies have demonstrated that besides the classic canonical transient receptor potential channel family, Orai family and stromal interaction molecule 1 (STIM1) might also be involved in the regulation of store-operated calcium channels (SOCCs). An increase in cytosolic free Ca2+ concentration promoted by store-operated Ca2+ entry (SOCE) in pulmonary arterial smooth muscle cells (PASMCs) is a major trigger for pulmonary vasoconstriction and proliferation and migration of PASMCs. In this study, our data revealed the following: (1) in both rat distal pulmonary arteries and PASMCs, chronic hypoxia exposure upregulated the expression of Orai1 and Orai2, without affecting Orai3 and STIM1; (2) either heterozygous knockout of HIF-1α in mice or knockdown of HIF-1α in PASMCs abolished the hypoxic upregulation of Orai2, but not Orai1, suggesting the hypoxic upregulation of Orai2 depends on HIF-1α; and (3) using small interference RNA knockdown strategies, Orai1, 2, 3 and STIM1 were all shown to mediate SOCE in hypoxic PASMCs...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/29152908/the-genetics-of-kawasaki-disease
#11
Yoshihiro Onouchi
Kawasaki disease (KD) is a complex disorder which affects genetically susceptible infants and children. Several susceptibility genes (e.g., ITPKC, CASP3, CD40 and ORAI) and chromosomal regions have been identified through genome-wide association and genome-wide linkage studies to have association with KD. Knowledge of susceptibility genes involved in the pathogenesis of KD may provide new insights into diagnosis and treatment of this condition. However, there is much that we still do not know about the genetic basis of KD...
November 19, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/29024298/detailed-evidence-for-an-unparalleled-interaction-mode-between-calmodulin-and-orai-proteins
#12
Lukas Traxler, Petr Rathner, Marc Fahrner, Michael Stadlbauer, Felix Faschinger, Tatsiana Charnavets, Norbert Müller, Christoph Romanin, Peter Hinterdorfer, Hermann J Gruber
Calmodulin (CaM) binds most of its targets by wrapping around an amphipathic α-helix. The N-terminus of Orai proteins contains a conserved CaM-binding segment but the binding mechanism has been only partially characterized. Here, microscale thermophoresis (MST), surface plasmon resonance (SPR), and atomic force microscopy (AFM) were employed to study the binding equilibria, the kinetics, and the single-molecule interaction forces involved in the binding of CaM to the conserved helical segments of Orai1 and Orai3...
October 11, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/29016923/surface-morphology-and-dislocation-characteristics-near-the-surface-of-4h-sic-wafer-using-multi-directional-scanning-transmission-electron-microscopy
#13
Takahiro Sato, Yoshihisa Orai, Yuya Suzuki, Hiroyuki Ito, Toshiyuki Isshiki, Munetoshi Fukui, Kuniyasu Nakamura, C T Schamp
To improve the reliability of silicon carbide (SiC) electronic power devices, the characteristics of various kinds of crystal defects should be precisely understood. Of particular importance is understanding the correlation between the surface morphology and the near surface dislocations. In order to analyze the dislocations near the surface of 4H-SiC wafers, a dislocation analysis protocol has been developed. This protocol consists of the following process: (1) inspection of surface defects using low energy scanning electron microscopy (LESEM), (2) identification of small and shallow etch pits using KOH low temperature etching, (3) classification of etch pits using LESEM, (4) specimen preparation of several hundred nanometer thick sample using the in-situ focused ion beam micro-sampling® technique, (5) crystallographic analysis using the selected diffraction mode of the scanning transmission electron microscope (STEM), and (6) determination of the Burgers vector using multi-directional STEM (MD-STEM)...
October 1, 2017: Microscopy
https://www.readbyqxmd.com/read/28974198/integrated-pipeline-for-inferring-the-evolutionary-history-of-a-gene-family-embedded-in-the-species-tree-a-case-study-on-the-stimate-gene-family
#14
Jia Song, Sisi Zheng, Nhung Nguyen, Youjun Wang, Yubin Zhou, Kui Lin
BACKGROUND: Because phylogenetic inference is an important basis for answering many evolutionary problems, a large number of algorithms have been developed. Some of these algorithms have been improved by integrating gene evolution models with the expectation of accommodating the hierarchy of evolutionary processes. To the best of our knowledge, however, there still is no single unifying model or algorithm that can take all evolutionary processes into account through a stepwise or simultaneous method...
October 3, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28958825/evaluation-of-different-screening-tools-for-predicting-femoral-neck-osteoporosis-in-rural-south-indian-postmenopausal-women
#15
Kripa Elizabeth Cherian, Nitin Kapoor, Sahana Shetty, Dukhabandhu Naik, Nihal Thomas, Thomas V Paul
The measurement of bone mineral density by dual-energy X-ray absorptiometry scan is the "gold standard" for the diagnosis of osteoporosis, which has limited availability in many parts of India. This study was done to assess the diagnostic performance of 6 internationally validated tools (Simple Calculated Osteoporosis Risk Estimation [SCORE], age, bulk, one or never estrogen [ABONE], Osteoporosis Risk Assessment Instrument [ORAI] and Osteoporosis Self-Assessment Tool for Asians [OSTA], Fracture Risk Assessment Tool [FRAX®], and calcaneal quantitative ultrasound [QUS]) for the diagnosis of osteoporosis at the femoral neck (FN)...
September 25, 2017: Journal of Clinical Densitometry
https://www.readbyqxmd.com/read/28930597/the-store-operated-calcium-channels-in-cancer-metastasis-from-cell-migration-invasion-to-metastatic-colonization
#16
Pingli Mo, Shengyu Yang
Store-operated calcium entry (SOCE) is the predominant calcium entry mechanism in most cancer cells. SOCE is mediated by the endoplasmic reticulum calcium sensor STIMs (STIM1 and 2) and plasma membrane channel forming unit Orais (Orai 1-3). In recent years there is increasing evidence indicating that SOCE in cancer cells is dysregulated to promote cancer cell migration, invasion and metastasis. The overexpression of STIM and Orai proteins has been reported to correlate with the metastatic progression of various cancers...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28912430/stim1-dependent-ca-2-signaling-regulates-podosome-formation-to-facilitate-cancer-cell-invasion
#17
Yun-Wen Chen, Yih-Fung Chen, Wen-Tai Chiu, Hong-Chen Chen, Meng-Ru Shen
The clinical significance of STIM proteins and Orai Ca(2+) channels in tumor progression has been demonstrated in different types of cancers. Podosomes are dynamic actin-rich cellular protrusions that facilitate cancer cell invasiveness by degrading extracellular matrix. Whether STIM1-dependent Ca(2+) signaling facilitates cancer cell invasion through affecting podosome formation remains unclear. Here we show that the invasive fronts of cancer tissues overexpress STIM1, accompanied by active store-operated Ca(2+) entry (SOCE)...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28900932/neurological-and-motor-disorders-neuronal-store-operated-ca-2-signaling-an-overview-and-its-function
#18
Sunitha Bollimuntha, Biswaranjan Pani, Brij B Singh
Calcium (Ca(2+)) is a ubiquitous second messenger that performs significant physiological task such as neurosecretion, exocytosis, neuronal growth/differentiation, and the development and/or maintenance of neural circuits. An important regulatory aspect of neuronal Ca(2+) homeostasis is store-operated Ca(2+) entry (SOCE) which, in recent years, has gained much attention for influencing a variety of nerve cell responses. Essentially, activation of SOCE ensues following the activation of the plasma membrane (PM) store-operated Ca(2+) channels (SOCC) triggered by the depletion of endoplasmic reticulum (ER) Ca(2+) stores...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900927/cardiovascular-and-hemostatic-disorders-role-of-stim-and-orai-proteins-in-vascular-disorders
#19
Jyoti Tanwar, Mohamed Trebak, Rajender K Motiani
Store-operated Ca(2+) entry (SOCE) mediated by STIM and Orai proteins is a highly regulated and ubiquitous signaling pathway that plays an important role in various cellular and physiological functions. Endoplasmic reticulum (ER) serves as the major site for intracellular Ca(2+) storage. Stromal Interaction Molecule 1/2 (STIM1/2) sense decrease in ER Ca(2+) levels and transmits the message to plasma membrane Ca(2+) channels constituted by Orai family members (Orai1/2/3) resulting in Ca(2+) influx into the cells...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900924/tissue-specificity-store-operated-ca-2-entry-in-cardiac-myocytes
#20
Martin D Bootman, Katja Rietdorf
Calcium (Ca(2+)) is a key regulator of cardiomyocyte contraction. The Ca(2+) channels, pumps, and exchangers responsible for the cyclical cytosolic Ca(2+) signals that underlie contraction are well known. In addition to those Ca(2+) signaling components responsible for contraction, it has been proposed that cardiomyocytes express channels that promote the influx of Ca(2+) from the extracellular milieu to the cytosol in response to depletion of intracellular Ca(2+) stores. With non-excitable cells, this store-operated Ca(2+) entry (SOCE) is usually easily demonstrated and is essential for prolonging cellular Ca(2+) signaling and for refilling depleted Ca(2+) stores...
2017: Advances in Experimental Medicine and Biology
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