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https://www.readbyqxmd.com/read/27881772/store-operated-calcium-channel-complex-in-postsynaptic-spines-a-new-therapeutic-target-for-alzheimer-s-disease-treatment
#1
Hua Zhang, Suya Sun, Lili Wu, Ekaterina Pchitskaya, Olga Zakharova, Klementina Fon Tacer, Ilya Bezprozvanny
: Mushroom dendritic spine structures are essential for memory storage and the loss of mushroom spines may explain memory defects in aging and Alzheimer's disease (AD). The stability of mushroom spines depends on stromal interaction molecule 2 (STIM2)-mediated neuronal-store-operated Ca(2+) influx (nSOC) pathway, which is compromised in AD mouse models, in aging neurons, and in sporadic AD patients. Here, we demonstrate that the Transient Receptor Potential Canonical 6 (TRPC6) and Orai2 channels form a STIM2-regulated nSOC Ca(2+) channel complex in hippocampal mushroom spines...
November 23, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27865925/orai1-and-orai2-mediate-store-operated-calcium-entry-that-regulates-hl60-cell-migration-and-fak-phosphorylation
#2
R Diez-Bello, I Jardin, G M Salido, J A Rosado
Store-operated Ca(2+) entry (SOCE) is a major mechanism for the regulation of intracellular Ca(2+) homeostasis and cellular function. Emerging evidence has revealed that altered expression and function of the molecular determinants of SOCE play a critical role in the development or maintenance of several cancer hallmarks, including enhanced proliferation and migration. Here we show that, in the acute myeloid leukemia cell line HL60, Orai2 is highly expressed at the transcript level, followed by the expression of Orai1...
November 16, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27617218/identification-of-trpcs-genetic-variants-that-modify-risk-for-lung-cancer-based-on-the-pathway-and-two-stage-study
#3
Zili Zhang, Jian Wang, Jianxing He, Xiansheng Zeng, Xindong Chen, Mingmei Xiong, Qipeng Zhou, Meihua Guo, Defu Li, Wenju Lu
OBJECTIVE: Store operated calcium channels (SOCCs) and Receptor-operated calcium channels (ROCCs) are important pathways participating in regulation of intracellular Ca(2 +) concentration in various cell types. The purpose of our study is to determine whether genetic variations in key components of SOCCs and ROCCs are associated with lung cancer risk. METHODS: We identified 236 tagSNPs in 9 key genes related to SOCCs and ROCCs (TRPC1, TRPC3, TRPC4, TRPC6, TRPC7, ORAI1, ORAI2, STIM1, and STIM2) and evaluated their association with lung cancer risk in a two-stage case-control study with a total of 2433 lung cancer cases and 2433 cancer-free controls using Illumina high throughput genotyping platform...
September 2016: Meta Gene
https://www.readbyqxmd.com/read/27235552/hypoxic-stress-up-regulates-kir2-1-expression-and-facilitates-cell-proliferation-in-brain-capillary-endothelial-cells
#4
Hideto Yamamura, Yoshiaki Suzuki, Hisao Yamamura, Kiyofumi Asai, Yuji Imaizumi
The blood-brain barrier (BBB) is mainly composed of brain capillary endothelial cells (BCECs), astrocytes and pericytes. Brain ischemia causes hypoxic encephalopathy and damages BBB. However, it remains still unclear how hypoxia affects BCECs. In the present study, t-BBEC117 cells, an immortalized bovine brain endothelial cell line, were cultured under hypoxic conditions at 4-5% oxygen for 72 h. This hypoxic stress caused hyperpolarization of resting membrane potential. Patch-clamp recordings revealed a marked increase in Ba(2+)-sensitive inward rectifier K(+) current in t-BBEC117 cells after hypoxic culture...
August 5, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27041216/redox-modulation-of-stim-orai-signaling
#5
REVIEW
Rajesh Bhardwaj, Matthias A Hediger, Nicolas Demaurex
STIM1 and ORAI1 constitute the core machinery of the ubiquitous store-operated calcium entry pathway and loss of function in these proteins is associated with severe immune and muscular disorders. Other isoforms-STIM1L, STIM2, ORAI2 and ORAI3 exhibit varied expression levels in different cell types along with several other interaction partners and thereby play different roles to facilitate, regulate and fine-tune the calcium entry. STIM proteins convey the Ca(2+) store-depletion message to the PM and thereby participate in refilling of the ER by physically interacting with the Ca(2+)-selective ORAI channels at the PM...
August 2016: Cell Calcium
https://www.readbyqxmd.com/read/26515404/dental-enamel-cells-express-functional-soce-channels
#6
Meerim K Nurbaeva, Miriam Eckstein, Axel R Concepcion, Charles E Smith, Sonal Srikanth, Michael L Paine, Yousang Gwack, Michael J Hubbard, Stefan Feske, Rodrigo S Lacruz
Dental enamel formation requires large quantities of Ca(2+) yet the mechanisms mediating Ca(2+) dynamics in enamel cells are unclear. Store-operated Ca(2+) entry (SOCE) channels are important Ca(2+) influx mechanisms in many cells. SOCE involves release of Ca(2+) from intracellular pools followed by Ca(2+) entry. The best-characterized SOCE channels are the Ca(2+) release-activated Ca(2+) (CRAC) channels. As patients with mutations in the CRAC channel genes STIM1 and ORAI1 show abnormal enamel mineralization, we hypothesized that CRAC channels might be an important Ca(2+) uptake mechanism in enamel cells...
October 30, 2015: Scientific Reports
https://www.readbyqxmd.com/read/26218135/stim-and-orai-proteins-in-the-nervous-system
#7
REVIEW
Robert Kraft
Stromal interaction molecules (STIM) 1 and 2 are sensors of the calcium concentration in the endoplasmic reticulum. Depletion of endoplasmic reticulum calcium stores activates STIM proteins which, in turn, bind and open calcium channels in the plasma membrane formed by the proteins ORAI1, ORAI2, and ORAI3. The resulting store-operated calcium entry (SOCE), mostly controlled by the principal components STIM1 and ORAI1, has been particularly characterized in immune cells. In the nervous system, all STIM and ORAI homologs are expressed...
2015: Channels
https://www.readbyqxmd.com/read/26177720/orai-cracm1-and-kca3-1-ion-channels-interact-in-the-human-lung-mast-cell-plasma-membrane
#8
S Mark Duffy, Ian Ashmole, Dawn T Smallwood, Mark L Leyland, Peter Bradding
BACKGROUND: Orai/CRACM1 ion channels provide the major Ca(2+) influx pathway for FcεRI-dependent human lung mast cell (HLMC) mediator release. The Ca(2+)-activated K(+) channel KCa3.1 modulates Ca(2+) influx and the secretory response through hyperpolarisation of the plasma membrane. We hypothesised that there is a close functional and spatiotemporal interaction between these Ca(2+)- and K(+)-selective channels. RESULTS: Activation of FcεRI-dependent HLMC KCa3...
July 16, 2015: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/25964739/stim-and-orai-proteins-in-neuronal-ca-2-signaling-and-excitability
#9
REVIEW
Francesco Moccia, Estella Zuccolo, Teresa Soda, Franco Tanzi, Germano Guerra, Lisa Mapelli, Francesco Lodola, Egidio D'Angelo
Stim1 and Orai1 are ubiquitous proteins that have long been known to mediate Ca(2+) release-activated Ca(2+) (CRAC) current (ICRAC) and store-operated Ca(2+) entry (SOCE) only in non-excitable cells. SOCE is activated following the depletion of the endogenous Ca(2+) stores, which are mainly located within the endoplasmic reticulum (ER), to replete the intracellular Ca(2+) reservoir and engage specific Ca(2+)-dependent processes, such as proliferation, migration, cytoskeletal remodeling, and gene expression...
2015: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/25791427/facilitation-of-orai3-targeting-and-store-operated-function-by-orai1
#10
Dalia Alansary, Ivan Bogeski, Barbara A Niemeyer
Orai1 subunits interacting with STIM1 molecules comprise the major components responsible for calcium release-activated calcium (CRAC) channels. The homologs Orai2 and Orai3 yield smaller store-operated currents when overexpressed and are mostly unable to substitute Orai1. Orai3 subunits are also essential components of store independent channel complexes and also tune inhibition of ICRAC by reactive oxygen species. Here we use patch-clamp, microscopy, Ca(2+)-imaging and biochemical experiments to investigate the interdependence of Orai2, Orai3 and Orai1...
July 2015: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/25769459/orai1-orai2-complex-is-involved-in-store-operated-calcium-entry-in-chondrocyte-cell-lines
#11
Munenori Inayama, Yoshiaki Suzuki, Satoshi Yamada, Takashi Kurita, Hisao Yamamura, Susumu Ohya, Wayne R Giles, Yuji Imaizumi
Ca(2+) influx via store-operated Ca(2+) entry (SOCE) plays critical roles in many essential cellular functions. The Ca(2+) release-activated Ca(2+) (CRAC) channel complex, consisting of Orai and STIM, is one of the major components of store-operated Ca(2+) (SOC) channels. Our previous study demonstrated that histamine can cause sustained Ca(2+) entry through SOC channels in OUMS-27 cells derived from human chondrosarcoma. This SOCE was increased by low- and decreased by high-concentrations of 2-aminoethoxydiphenyl borate...
May 2015: Cell Calcium
https://www.readbyqxmd.com/read/25748572/regulation-of-store-operated-ca2-entry-activity-by-cell-cycle-dependent-up-regulation-of-orai2-in-brain-capillary-endothelial-cells
#12
Hiroaki Kito, Hisao Yamamura, Yoshiaki Suzuki, Hideto Yamamura, Susumu Ohya, Kiyofumi Asai, Yuji Imaizumi
Store-operated Ca(2+) entry (SOCE) via Orai1 and STIM1 complex is supposed to have obligatory roles in the regulation of cellular functions of vascular endothelial cells, while little is known about the contribution of Orai2. Quantitative PCR and Western blot analyses indicated the expression of Orai2 and STIM2, in addition to Orai1 and STIM1 in bovine brain capillary endothelial cell line, t-BBEC117. During the exponential growth of t-BBEC117, the knockdown of Orai1 and STIM1 significantly reduced the SOCE activity, whereas Orai2 and STIM2 siRNAs had no effect...
April 10, 2015: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/25673771/upregulated-expression-of-stim2-trpc6-and-orai2-contributes-to-the-transition-of-pulmonary-arterial-smooth-muscle-cells-from-a-contractile-to-proliferative-phenotype
#13
Ruby A Fernandez, Jun Wan, Shanshan Song, Kimberly A Smith, Yali Gu, Mohammad Tauseef, Haiyang Tang, Ayako Makino, Dolly Mehta, Jason X-J Yuan
Pulmonary arterial hypertension (PAH) is a progressive disease that, if left untreated, eventually leads to right heart failure and death. Elevated pulmonary arterial pressure (PAP) in patients with PAH is mainly caused by an increase in pulmonary vascular resistance (PVR). Sustained vasoconstriction and excessive pulmonary vascular remodeling are two major causes for elevated PVR in patients with PAH. Excessive pulmonary vascular remodeling is mediated by increased proliferation of pulmonary arterial smooth muscle cells (PASMC) due to PASMC dedifferentiation from a contractile or quiescent phenotype to a proliferative or synthetic phenotype...
April 15, 2015: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/25459299/potent-functional-uncoupling-between-stim1-and-orai1-by-dimeric-2-aminodiphenyl-borinate-analogs
#14
COMPARATIVE STUDY
Eunan Hendron, Xizhuo Wang, Yandong Zhou, Xiangyu Cai, Jun-ichi Goto, Katsuhiko Mikoshiba, Yoshihiro Baba, Tomohiro Kurosaki, Youjun Wang, Donald L Gill
The coupling of ER Ca(2+)-sensing STIM proteins and PM Orai Ca(2+) entry channels generates "store-operated" Ca(2+) signals crucial in controlling responses in many cell types. The dimeric derivative of 2-aminoethoxydiphenyl borinate (2-APB), DPB162-AE, blocks functional coupling between STIM1 and Orai1 with an IC50 (200 nM) 100-fold lower than 2-APB. Unlike 2-APB, DPB162-AE does not affect L-type or TRPC channels or Ca(2+) pumps at maximal STIM1-Orai1 blocking levels. DPB162-AE blocks STIM1-induced Orai1 or Orai2, but does not block Orai3 or STIM2-mediated effects...
December 2014: Cell Calcium
https://www.readbyqxmd.com/read/25451082/regulation-of-phagocytosis-and-cytokine-secretion-by-store-operated-calcium-entry-in-primary-isolated-murine-microglia
#15
Dae Keon Heo, Hye Min Lim, Joo Hyun Nam, Min Goo Lee, Joo Young Kim
Microglia are immune effector cells in the central nervous system that participate in tissue repair, inflammatory responses, and neuronal degeneration. The most important signaling factor in the differentiation of immune-active cells after stimulation is the sustained high calcium concentration in the cytosol, which is called store-operated calcium entry (SOCE). Recently, the molecular identity of the store-operated channel (SOC) has revealed that Orai1, Orai2, Orai3, Stim1, and Stim2 constitute the most of SOC...
January 2015: Cellular Signalling
https://www.readbyqxmd.com/read/25143380/a-reciprocal-shift-in-transient-receptor-potential-channel-1-trpc1-and-stromal-interaction-molecule-2-stim2-contributes-to-ca2-remodeling-and-cancer-hallmarks-in-colorectal-carcinoma-cells
#16
Diego Sobradillo, Miriam Hernández-Morales, Daniel Ubierna, Mary P Moyer, Lucía Núñez, Carlos Villalobos
We have investigated the molecular basis of intracellular Ca(2+) handling in human colon carcinoma cells (HT29) versus normal human mucosa cells (NCM460) and its contribution to cancer features. We found that Ca(2+) stores in colon carcinoma cells are partially depleted relative to normal cells. However, resting Ca(2+) levels, agonist-induced Ca(2+) increases, store-operated Ca(2+) entry (SOCE), and store-operated currents (ISOC) are largely enhanced in tumor cells. Enhanced SOCE and depleted Ca(2+) stores correlate with increased cell proliferation, invasion, and survival characteristic of tumor cells...
October 17, 2014: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/24834055/stim-and-orai-isoform-expression-in-pregnant-human-myometrium-a-potential-role-in-calcium-signaling-during-pregnancy
#17
Evonne C Chin-Smith, Donna M Slater, Mark R Johnson, Rachel M Tribe
Store-operated calcium (Ca(2+)) entry (SOCE) can be mediated by two novel proteins, STIM/Orai. We have previously demonstrated that members of the TRPC family, putative basal and store operated calcium entry channels, are present in human myometrium and regulated by labor associated stimuli IL-1β and mechanical stretch. Although STIM and Orai isoforms (1-3) have been reported in other smooth muscle cell types, there is little known about the expression or gestational regulation of STIM and Orai expression in human myometrium...
2014: Frontiers in Physiology
https://www.readbyqxmd.com/read/24670147/the-ryanodine-receptor-agonist-4-chloro-3-ethylphenol-blocks-orai-store-operated-channels
#18
Bo Zeng, Gui-Lan Chen, Nikoleta Daskoulidou, Shang-Zhong Xu
BACKGROUND: Depletion of the Ca(2+) store by ryanodine receptor (RyR) agonists induces store-operated Ca(2+) entry (SOCE). 4-Chloro-3-ethylphenol (4-CEP) and 4-chloro-m-cresol (4-CmC) are RyR agonists commonly used as research tools and diagnostic reagents for malignant hyperthermia. Here, we investigated the effects of 4-CEP and its analogues on SOCE. EXPERIMENTAL APPROACH: SOCE and ORAI1-3 currents were recorded by Ca(2+) imaging and whole-cell patch recordings in rat L6 myoblasts and in HEK293 cells overexpressing STIM1/ORAI1-3...
March 2014: British Journal of Pharmacology
https://www.readbyqxmd.com/read/24603752/enhanced-expression-of-stim-orai-and-trpc-transcripts-and-proteins-in-endothelial-progenitor-cells-isolated-from-patients-with-primary-myelofibrosis
#19
Silvia Dragoni, Umberto Laforenza, Elisa Bonetti, Marta Reforgiato, Valentina Poletto, Francesco Lodola, Cinzia Bottino, Daniele Guido, Alessandra Rappa, Sumedha Pareek, Mario Tomasello, Maria Rosa Guarrera, Maria Pia Cinelli, Adele Aronica, Germano Guerra, Giovanni Barosi, Franco Tanzi, Vittorio Rosti, Francesco Moccia
BACKGROUND: An increase in the frequency of circulating endothelial colony forming cells (ECFCs), the only subset of endothelial progenitor cells (EPCs) truly belonging to the endothelial phenotype, occurs in patients affected by primary myelofibrosis (PMF). Herein, they might contribute to the enhanced neovascularisation of fibrotic bone marrow and spleen. Store-operated Ca2+ entry (SOCE) activated by the depletion of the inositol-1,4,5-trisphosphate (InsP3)-sensitive Ca2+ store drives proliferation in ECFCs isolated from both healthy donors (N-ECFCs) and subjects suffering from renal cellular carcinoma (RCC-ECFCs)...
2014: PloS One
https://www.readbyqxmd.com/read/24040356/the-contribution-of-orai-cracm-1-and-orai-cracm-2-channels-in-store-operated-ca2-entry-and-mediator-release-in-human-lung-mast-cells
#20
Ian Ashmole, S Mark Duffy, Mark L Leyland, Peter Bradding
BACKGROUND: The influx of extracellular Ca(2+) into mast cells is critical for the FcεR1-dependent release of preformed granule-derived mediators and newly synthesised autacoids and cytokines. The Orai(CRACM) ion channel family provide the major pathway through which this Ca(2+) influx occurs. However the individual role of each of the three members of the Orai channel family in Ca(2+) influx and mediator release has not been defined in human mast cells. OBJECTIVE: To assess whether there might be value in targeting individual Orai family members for the inhibition of FcεRI-dependent human lung mast cells (HLMC) mediator release...
2013: PloS One
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