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S L Huang, L X Yang, S J Yang, R W Guo
Objective: To investigate the role of ORAI1 in the balloon injury-induced rat carotid artery neointimal formation and the relationship between ORAI1 and sodium and calcium exchanger(NCX)1. Methods: According to condition of carotid artery balloon injury and observation time, Sprague Dawley rats were divided into 3 groups including sham group, 7 days injury group, and 14 day injury group(n=3 each). According to virus of transfection, Sprague Dawley rats were divided into 2 groups including negative control group (negative lentiviruses particles transfection after establishment of carotid artery balloon injury model, n=3) and siORAI1 group(siORAI1 transfection after operation, n=3)...
November 24, 2016: Zhonghua Xin Xue Guan Bing za Zhi
Trevor J Shuttleworth
No abstract text is available yet for this article.
November 4, 2016: Cell Calcium
Michelle Yen, Ludmila A Lokteva, Richard S Lewis
Store-operated Ca(2+) entry occurs through the binding of the endoplasmic reticulum (ER) Ca(2+) sensor STIM1 to Orai1, the pore-forming subunit of the Ca(2+) release-activated Ca(2+) (CRAC) channel. Although the essential steps leading to channel opening have been described, fundamental questions remain, including the functional stoichiometry of the CRAC channel. The crystal structure of Drosophila Orai indicates a hexameric stoichiometry, while studies of linked Orai1 concatemers and single-molecule photobleaching suggest that channels assemble as tetramers...
November 1, 2016: Biophysical Journal
Xiangyu Cai, Yandong Zhou, Robert M Nwokonko, Natalia A Loktionova, Xianming Wang, Ping Xin, Mohamed Trebak, Youjun Wang, Donald L Gill
Orai channels mediate store-operated Ca2+ signals crucial in regulating transcription in many cell types, and implicated in numerous immunological and inflammatory disorders. Despite their central importance, controversy surrounds the basic subunit structure of Orai channels, several biochemical and biophysical studies suggesting a tetrameric structure yet crystallographic evidence indicating a hexamer. We systematically investigated the subunit configuration of the functional Orai1 channel, generating a series of tdTomato-tagged concatenated Orai1 channel constructs (dimers to hexamers) expressed in CRISPR-derived Orai1-knockout HEK cells, stably expressing STIM1-YFP...
October 25, 2016: Journal of Biological Chemistry
Ming Wei, Yandong Zhou, Aomin Sun, Guolin Ma, Lian He, Lijuan Zhou, Shuce Zhang, Jin Liu, Shenyuan L Zhang, Donald L Gill, Youjun Wang
Store-operated Ca(2+) entry (SOCE) mediated by STIM1 and Orai1 is crucial for Ca(2+) signaling and homeostasis in most cell types. 2-Aminoethoxydiphenyl borate (2-APB) is a well-described SOCE inhibitor, but its mechanisms of action remain largely elusive. Here, we show that 2-APB does not affect the dimeric state of STIM1, but enhances the intramolecular coupling between the coiled-coil 1 (CC1) and STIM-Orai-activating region (SOAR) of STIM1, with subsequent reduction in the formation of STIM1 puncta in the absence of Orai1 overexpression...
November 2016: Pflügers Archiv: European Journal of Physiology
S Indhavivadhana, M Rattanachaiyanont, S Angsuwathana, K Techatraisak, P Tanmahasamut, P Leerasiri
OBJECTIVES: To validate osteoporosis risk assessment tools in middle-aged Thai women. METHODS: A total of 1038 women who had bone mineral density (BMD) measurements using dual-energy X-ray absorptiometry were reviewed. Clinical data were used to validate the diagnostic test performance of various osteoporosis risk assessment tools, including ABONE, FRAX(®), ORAI, OSIRIS, SCORE, SOFSURF, and OSTA. The following parameters were evaluated: sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy; those with 95% confidence interval (CI) of the receiver operator characteristics area under the curve (ROC-AUC) > 0...
September 24, 2016: Climacteric: the Journal of the International Menopause Society
Benjamin Chun-Kit Tong, Claire Shuk-Kwan Lee, Wing-Hei Cheng, Kwok-On Lai, J Kevin Foskett, King-Ho Cheung
Some forms of familial Alzheimer's disease (FAD) are caused by mutations in presenilins (PSs), catalytic components of a γ-secretase complex that cleaves target proteins, including amyloid precursor protein (APP). Calcium (Ca(2+)) dysregulation in cells with these FAD-causing PS mutants has been attributed to attenuated store-operated Ca(2+) entry [SOCE; also called capacitative Ca(2+) entry (CCE)]. CCE occurs when STIM1 detects decreases in Ca(2+) in the endoplasmic reticulum (ER) and activates ORAI channels to replenish Ca(2+) stores in the ER...
September 6, 2016: Science Signaling
Sumita Chakraborty, Bipan K Deb, Tetyana Chorna, Vera Konieczny, Colin W Taylor, Gaiti Hasan
Store-operated Ca(2+) entry (SOCE) occurs when loss of Ca(2+) from the endoplasmic reticulum (ER) stimulates the Ca(2+) sensor, STIM, to cluster and activate the plasma membrane Ca(2+) channel Orai (encoded by Olf186-F in flies). Inositol 1,4,5-trisphosphate receptors (IP3Rs, which are encoded by a single gene in flies) are assumed to regulate SOCE solely by mediating ER Ca(2+) release. We show that in Drosophila neurons, mutant IP3R attenuates SOCE evoked by depleting Ca(2+) stores with thapsigargin. In normal neurons, store depletion caused STIM and the IP3R to accumulate near the plasma membrane, association of STIM with Orai, clustering of STIM and Orai at ER-plasma-membrane junctions and activation of SOCE...
October 15, 2016: Journal of Cell Science
Susana Cubillos, Johannes Norgauer
Psoriasis is an inflammatory skin disease with or without joint involvement. In this disease, the thickened epidermis and impaired barrier are associated with altered calcium gradients. Calcium and vitamin D are known to play important roles in keratinocyte differentiation and bone metabolism. Intracellular calcium is regulated by calcium-sensing receptor (CASR), calcium release-activated calcium modulator (ORAI) and stromal interaction molecule (STIM). Other proteins modulated by vitamin D play important roles in calcium regulation e...
October 2016: International Journal of Molecular Medicine
Ayrton R Massaro, Gregory Y H Lippp
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, with an estimated prevalence of 1-2% in North America and Europe. The increased prevalence of AF in Latin America is associated with an ageing general population, along with poor control of key risk factors, including hypertension. As a result, stroke prevalence and associated mortality have increased dramatically in the region. Therefore, the need for effective anticoagulation strategies in Latin America is clear. The aim of this review is to provide a contemporary overview of anticoagulants for stroke prevention...
August 11, 2016: Arquivos Brasileiros de Cardiologia
Tomasz Wegierski, Kinga Gazda, Jacek Kuznicki
Familial Alzheimer's disease (FAD)-causing mutations in presenilins were shown to alter intracellular calcium dynamics, including store-operated calcium entry (SOCE). However, the involvement of FAD-linked amyloid precursor protein (APP) in SOCE remains controversial. Here, we used gain-of-function and loss-of-function approaches to shed light on this issue. We found that Jurkat cells, which exhibit prominent SOCE mediated by Orai channels, maintain low APP levels. The ectopic expression of APP, either with wildtype sequence or FAD-causing Swedish mutation, had no effect on SOCE induced by calcium store depletion with cyclopiazonic acid (CPA)...
September 23, 2016: Biochemical and Biophysical Research Communications
Mohammadreza Vafa, Sepideh Soltani, Farid Zayeri, Mahtab Niroomand, Azadeh Najarzadeh
BACKGROUND: The results of the studies on the effects of sodium on bone metabolism have been inconsistent. There is no definitive answer to the question of whether sodium restriction can be associated with a lower incidence of osteoporosis. What reinforces the necessity of designing this study is the lack of findings with the approach of examining the effects of sodium on bone in our country. METHODS: This was a cross-sectional study conducted on 185 retired female teachers aged 45 to 70...
2016: Medical Journal of the Islamic Republic of Iran
Jonathan Pacheco, Laura Dominguez, A Bohórquez-Hernández, Alexander Asanov, Luis Vaca
STIM1 and Orai1 are the main components of a widely conserved Calcium influx pathway known as store-operated calcium entry (SOCE). STIM1 is a calcium sensor, which oligomerizes and activates Orai channels when calcium levels drop inside the endoplasmic reticulum (ER). The series of molecular rearrangements that STIM1 undergoes until final activation of Orai1 require the direct exposure of the STIM1 domain known as SOAR (Stim Orai Activating Region). In addition to these complex molecular rearrangements, other constituents like lipids at the plasma membrane, play critical roles orchestrating SOCE...
2016: Scientific Reports
Ilaria Maccari, Renping Zhao, Martin Peglow, Karsten Schwarz, Ivan Hornak, Mathias Pasche, Ariel Quintana, Markus Hoth, Bin Qu, Heiko Rieger
Ca(2+) microdomains and spatially resolved Ca(2+) signals are highly relevant for cell function. In T cells, local Ca(2+) signaling at the immunological synapse (IS) is required for downstream effector functions. We present experimental evidence that the relocation of the MTOC towards the IS during polarization drags mitochondria along with the microtubule network. From time-lapse fluorescence microscopy we conclude that mitochondria rotate together with the cytoskeleton towards the IS. We hypothesize that this movement of mitochondria towards the IS together with their functionality of absorption and spatial redistribution of Ca(2+) is sufficient to significantly increase the cytosolic Ca(2+) concentration...
July 7, 2016: Cell Calcium
Jianling Xia, Hongqiang Wang, Hongxiang Huang, Li Sun, Shaoting Dong, Na Huang, Min Shi, Jianping Bin, Yulin Liao, Wangjun Liao
ORAI calcium release-activated calcium modulator 1 (Orai1)- and stromal interacting molecule 1 (STIM1)-mediated store-operated Ca(2+) entry (SOCE) have been increasingly implicated in tumor progression; however, its role in gastric cancer (GC) is not well elucidated. We aimed to determine whether SOCE influences GC prognosis and elucidate the underlying mechanisms. Orai1 and STIM1 expressions were higher in GC tissues compared to adjacent non-tumor tissues according to RT-PCR and western blotting. Higher Orai1 and/or STIM1 expression was associated with more advanced disease, more frequent recurrence, and higher mortality rates in our study of 327 GC patients...
October 10, 2016: Cancer Letters
Robert Hooper, M Raza Zaidi, Jonathan Soboloff
Calcium is a key regulator of many physiological processes that are perturbed in cancer, such as migration, proliferation and apoptosis. The proteins STIM and Orai mediate store-operated calcium entry (SOCE), the main pathway for calcium entry in non-excitable cells. Changes in the expression and function of STIM and Orai have been found in a range of cancer types and thus implicated in disease progression. Here we discuss the role of STIM, Orai and the SOCE pathway in the progression of melanoma and explore how the heterogeneous nature of melanoma may explain the lack of consensus in the field regarding the role of SOCE in the progression of this disease...
August 2016: Science China. Life Sciences
Francesco Moccia, Estella Zuccolo, Valentina Poletto, Ilaria Turin, Germano Guerra, Paolo Pedrazzoli, Vittorio Rosti, Camillo Porta, Daniela Montagna
An increase in intracellular Ca2+ concentration plays a key role in the establishment of many cancer hallmarks, including aberrant proliferation, migration, invasion, resistance to apoptosis and angiogenesis. The dysregulation of Ca2+ entry is one of the most subtle mechanisms by which cancer cells overwhelm their normal counterparts and gain the adaptive advantages that result in tumour growth, vascularisation and dissemination throughout the organism. Both constitutive and agonist-induced Ca2+ influx may be mediated by store-dependent as well as store-independent Ca2+ entry routes...
2016: Current Medicinal Chemistry
Carolina Justus Buhrer Ferreira, Caroline Koga Plodek, Franciny Kossemba Soares, Rayza Assis de Andrade, Fernanda Teleginski, Maria Dagmar da Rocha
OBJECTIVE: to analyze the impact of guidelines regarding errors in medications prescribed for administration through enteral tubes. METHOD: quantitative study, in three phases, undertaken in internal medicine, neurology and an intensive care unit in a general teaching hospital. In Phase 1, the following was undertaken: a protocol for dilution and unit-dose repackaging and administration for 294 medications via enteral tubes; a decision flowchart; operational-standard procedures for dilution and unit-dose repackaging of oral pharmaceutical forms and for administration of medications through enteral tubes...
2016: Revista Latino-americana de Enfermagem
Martin Vaeth, Miriam Eckstein, Patrick J Shaw, Lina Kozhaya, Jun Yang, Friederike Berberich-Siebelt, Robert Clancy, Derya Unutmaz, Stefan Feske
T follicular helper (Tfh) cells promote affinity maturation of B cells in germinal centers (GCs), whereas T follicular regulatory (Tfr) cells limit the GC reaction. Store-operated Ca(2+) entry (SOCE) through Ca(2+) release-activated Ca(2+) (CRAC) channels mediated by STIM and ORAI proteins is a fundamental signaling pathway in T lymphocytes. Conditional deletion of Stim1 and Stim2 genes in T cells abolished SOCE and strongly reduced antibody-mediated immune responses following viral infection caused by impaired differentiation and function of Tfh cells...
June 21, 2016: Immunity
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