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https://www.readbyqxmd.com/read/28928244/selective-inhibitory-effects-of-zinc-on-cell-proliferation-in-esophageal-squamous-cell-carcinoma-through-orai1
#1
Sangyong Choi, Chaochu Cui, Yanhong Luo, Sun-Hee Kim, Jae-Kyun Ko, Xiaofang Huo, Jianjie Ma, Li-Wu Fu, Rhonda F Souza, Irina Korichneva, Zui Pan
Zinc, an essential micronutrient, has a cancer preventive role. Zinc deficiency has been shown to contribute to the progression of esophageal cancer. Orai1, a store-operated Ca(2+) entry (SOCE) channel, was previously reported to be highly expressed in tumor tissues removed from patients with esophageal squamous cell carcinoma (ESCC) with poor prognosis, and elevation of its expression contributes to both hyperactive intracellular Ca(2+) oscillations and fast cell proliferation in human ESCC cells. However, the molecular basis of cancer preventive functions of zinc and its association with Orai1-mediated cell proliferation remains unknown...
September 19, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28921392/resveratrol-attenuates-high-glucose-induced-endothelial-cell-apoptosis-via-mediation-of-store-operated-calcium-entry
#2
Ting Lu, Dayan Zhou, Pan Gao, Liangyi Si, Qiang Xu
The aim of this study was to evaluate the influence of resveratrol on HG-induced calcium entry in islet microvascular (MS-1) endothelial cells. MS-1 cells were pretreated with resveratrol or 2-APB (an inhibitor of store-operated calcium entry) and then incubated with high glucose. Cell viability was determined using the cell counting kit-8 method. Reactive oxygen species, endothelial apoptosis, and NO production were detected by DHE probe, TUNEL detection, and nitrate reductase assay kit. Protein levels of SOCE were detected by western blotting...
September 18, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28919480/cholesterol-modulates-the-cellular-localization-of-orai1-channels-and-its-disposition-among-membrane-domains
#3
A Bohórquez-Hernández, Enrico Gratton, Jonathan Pacheco, Alexander Asanov, Luis Vaca
Store Operated Calcium Entry (SOCE) is one of the most important mechanisms for calcium mobilization in to the cell. Two main proteins sustain SOCE: STIM1 that acts as the calcium sensor in the endoplasmic reticulum (ER) and Orai1 responsible for calcium influx upon depletion of ER. There are many studies indicating that SOCE is modulated by the cholesterol content of the plasma membrane (PM). However, a myriad of questions remain unanswered concerning the precise molecular mechanism by which cholesterol modulates SOCE...
September 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28913175/regulation-of-endoplasmic-reticulum-mitochondria-ca-2-transfer-and-its-importance-for-anti-cancer-therapies
#4
REVIEW
Gaia Pedriali, Alessandro Rimessi, Luigi Sbano, Carlotta Giorgi, Mariusz R Wieckowski, Maurizio Previati, Paolo Pinton
Inter-organelle membrane contact sites are emerging as major sites for the regulation of intracellular Ca(2+) concentration and distribution. Here, extracellular stimuli operate on a wide array of channels, pumps, and ion exchangers to redistribute intracellular Ca(2+) among several compartments. The resulting highly defined spatial and temporal patterns of Ca(2+) movement can be used to elicit specific cellular responses, including cell proliferation, migration, or death. Plasma membrane (PM) also can directly contact mitochondria and endoplasmic reticulum (ER) through caveolae, small invaginations of the PM that ensure inter-organelle contacts, and can contribute to the regulation of numerous cellular functions through scaffolding proteins such as caveolins...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28912430/stim1-dependent-ca-2-signaling-regulates-podosome-formation-to-facilitate-cancer-cell-invasion
#5
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/28900935/metabolic-disorders-and-cancer-hepatocyte-store-operated-ca-2-channels-in-nonalcoholic-fatty-liver-disease
#6
Eunüs S Ali, Grigori Y Rychkov, Greg J Barritt
In steatotic hepatocytes, intracellular Ca(2+) homeostasis is substantially altered compared to normal. Decreased Ca(2+) in the endoplasmic reticulum (ER) can lead to ER stress, an important mediator of the progression of liver steatosis to nonalcoholic steatohepatitis, type 2 diabetes, and hepatocellular carcinoma. Store-operated Ca(2+) channels (SOCs) in hepatocytes are composed principally of Orai1 and STIM1 proteins. Their main role is the maintenance of adequate Ca(2+) in the lumen of the ER. In steatotic hepatocytes, store-operated Ca(2+) entry (SOCE) is substantially inhibited...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900934/fertility-store-operated-ca-2-entry-in-germ-cells-role-in-egg-activation
#7
Zoltan Machaty, Chunmin Wang, Kiho Lee, Lu Zhang
At the time of fertilization, the sperm activates the egg and induces embryonic development by triggering an elevation in the egg's intracellular free Ca(2+) concentration. In mammals the initial Ca(2+) rise is followed by a series of repetitive Ca(2+) transients (known as oscillations) that last for several hours. Although the source of Ca(2+) during the signaling process is primarily the egg's smooth endoplasmic reticulum, the oscillations stop in the absence of extracellular Ca(2+) indicating that a Ca(2+) influx across the plasma membrane is essential to sustain them...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900931/cardiac-remodeling-and-disease-current-understanding-of-stim1-orai1-mediated-store-operated-ca-2-entry-in-cardiac-function-and-pathology
#8
Fiona Bartoli, Jessica Sabourin
For a long time, Ca(2+) entry into cardiomyocytes was considered the sole domain of the L-type Ca(2+) channel. Recently, STIM1/Orai1-mediated store-operated Ca(2+) entry has been also reported to participate to Ca(2+) influx in cardiac cells and has emerged as a key player to alter Ca(2+) in the cardiomyocyte. In this review, we will highlight accumulated knowledge about the presence and the potential contribution of STIM1/Orai1-dependent SOCE to cardiac function and its role in the cardiac pathogenesis. Overall, even if STIM1/Orai1 proteins are present in the heart, contradictory results have been reported regarding their contribution to cardiac physiology and pathology, pointing out the necessity of further investigations, a major challenge over the coming years...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900930/cardiac-remodeling-and-disease-soce-and-trpc-signaling-in-cardiac-pathology
#9
Petra Eder
TRPC channels have been suggested as potential candidates mediating store-operated Ca(2+) entry (SOCE) in cardiomyocytes. There is increasing evidence that the TRPC isoforms TRPC1 and TRPC4 might fulfill the function as SOCs, in concert with or in parallel to the key players of SOCE, Orai1, and STIM1. Several other isoforms, e.g., TRPC3, TRPC6, and TRPC7, might rather associate to receptor-activated diacylglycerol (DAG)-sensitive ion channels. However, the exact activation mode has not been elucidated yet, given the characteristic of TRPC channels to heteromerize to unpredictable ion channel assemblies...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900928/cardiovascular-and-hemostatic-disorders-soce-and-ca-2-handling-in-platelet-dysfunction
#10
Jose J Lopez, Gines M Salido, Juan A Rosado
Among the Ca(2+) entry mechanisms in platelets, store-operated Ca(2+) entry (SOCE) plays a prominent role as it is necessary to achieve full activation of platelet functions and replenish intracellular Ca(2+) stores. In platelets, as in other non-excitable cells, SOCE has been reported to involve the activation of plasma membrane channels by the ER Ca(2+) sensor STIM1. Despite electrophysiological studies are not possible in human platelets, indirect analyses have revealed that the Ca(2+)-permeable channels involve Orai1 and, most likely, TRPC1 subunits...
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
#11
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/28900926/immunological-disorders-regulation-of-ca-2-signaling-in-t-lymphocytes
#12
Sonal Srikanth, Jin Seok Woo, Zuoming Sun, Yousang Gwack
Engagement of T cell receptors (TCRs) with cognate antigens triggers cascades of signaling pathways in helper T cells. TCR signaling is essential for the effector function of helper T cells including proliferation, differentiation, and cytokine production. It also modulates effector T cell fate by inducing cell death, anergy (nonresponsiveness), exhaustion, and generation of regulatory T cells. One of the main axes of TCR signaling is the Ca(2+)-calcineurin-nuclear factor of activated T cells (NFAT) signaling pathway...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900914/stim-trp-pathways-and-microdomain-organization-contribution-of-trpc1-in-store-operated-ca-2-entry-impact-on-ca-2-signaling-and-cell-function
#13
Hwei Ling Ong, Indu S Ambudkar
Store-operated calcium entry (SOCE) is a ubiquitous Ca(2+) entry pathway that is activated in response to depletion of ER-Ca(2+) stores and critically controls the regulation of physiological functions in a wide variety of cell types. The transient receptor potential canonical (TRPC) channels (TRPCs 1-7), which are activated by stimuli leading to PIP2 hydrolysis, were first identified as molecular components of SOCE channels. While TRPC1 was associated with SOCE and regulation of function in several cell types, none of the TRPC members displayed I CRAC, the store-operated current identified in lymphocytes and mast cells...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900910/the-stim-orai-pathway-conformational-coupling-between-stim-and-orai-in-the-activation-of-store-operated-ca-2-entry
#14
Robert M Nwokonko, Xiangyu Cai, Natalia A Loktionova, Youjun Wang, Yandong Zhou, Donald L Gill
Store-operated Ca(2+) entry fulfills a crucial role in controlling Ca(2+) signals in almost all cells. The Ca(2+)-sensing stromal interaction molecule (STIM) proteins in the endoplasmic reticulum (ER) undergo complex conformational changes in response to depleted ER luminal Ca(2+), allowing them to unfold and become trapped in ER-plasma membrane (PM) junctions. Dimers of STIM proteins trap and gate the plasma membrane Orai Ca(2+) channels within these junctions to generate discrete zones of high Ca(2+) and regulate sensitive Ca(2+)-dependent intracellular signaling pathways...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900908/the-stim-orai-pathway-orai-the-pore-forming-subunit-of-the-crac-channel
#15
Aparna Gudlur, Patrick G Hogan
This chapter focuses on the Orai proteins, Orai1-Orai3, with special emphasis on Orai1, in humans and other mammals, and on the definitive evidence that Orai is the pore subunit of the CRAC channel. It begins by reviewing briefly the defining characteristics of the CRAC channel, then discusses the studies that implicated Orai as part of the store-operated Ca(2+) entry pathway and as the CRAC channel pore subunit, and finally examines ongoing work that is providing insights into CRAC channel structure and gating...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900907/the-stim-orai-pathway-stim-orai-structures-isolated-and-in-complex
#16
Jinhui Zhu, Qingping Feng, Peter B Stathopulos
Considerable progress has been made elucidating the molecular mechanisms of calcium (Ca(2+)) sensing by stromal interaction molecules (STIMs) and the basis for Orai channel activity. This chapter focuses on the available high-resolution structural details of STIM and Orai proteins with respect to the regulation of store-operated Ca(2+) entry (SOCE). Solution structures of the Ca(2+)-sensing domains of STIM1 and STIM2 are reviewed in detail, crystal structures of cytosolic coiled-coil STIM fragments are discussed, and an overview of the closed Drosophila melanogaster Orai hexameric structure is provided...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28866365/store-operated-calcium-entry-is-dispensable-for-the-activation-of-erk1-2-pathway-in-prostate-cancer-cells
#17
Aida M Lopez-Guerrero, Carlos Pascual-Caro, Francisco Javier Martin-Romero, Eulalia Pozo-Guisado
STIM1, the endoplasmic reticulum Ca(2+) sensor that modulates the activity of plasma membrane Ca(2+) channels, becomes phosphorylated at ERK1/2 target sites during Ca(2+) store depletion triggered by thapsigargin or epidermal growth factor (EGF). This ERK1/2-dependent phosphorylation regulates STIM1 localization and dissociation from microtubules, and it is known that enhances the binding to ORAI1, a store-operated Ca(2+) entry (SOCE) channel, leading to the activation of this Ca(2+) influx pathway. However, there remained some evidence of a role for SOCE in the activation of ERK1/2, and here we assessed the contribution of SOCE to ERK1/2 activation by generating a STIM1-deficient cell line by CRISPR/Cas9 genome editing of the STIM1 locus in prostate cancer PC3 cells...
August 31, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28851859/regulation-of-orai1-stim1-mediated-icrac-by-intracellular-ph
#18
D Gavriliouk, N R Scrimgeour, S Grigoryev, L Ma, F H Zhou, G J Barritt, G Y Rychkov
Ca(2+) release activated Ca(2+) (CRAC) channels composed of two cellular proteins, Ca(2+)-sensing stromal interaction molecule 1 (STIM1) and pore-forming Orai1, are the main mediators of the Ca(2+) entry pathway activated in response to depletion of intracellular Ca(2+) stores. Previously it has been shown that the amplitude of CRAC current (ICRAC) strongly depends on extracellular and intracellular pH. Here we investigate the intracellular pH (pHi) dependence of ICRAC mediated by Orai1 and STIM1ectopically expressed in HEK293 cells...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28845932/-early-diagnosis-of-risk-for-developing-calcium-oxalate-urolithiasis
#19
O I Apolikhin, A V Sivkov, O V Konstantinova, P A Slominskii, T V Tupitsyna, D N Kalinichenko
AIM: To identify risk groups for calcium oxalate urolithiasis among healthy individuals and patients with urolithiasis in the Russian population using molecular genetics. MATERIALS AND METHODS: The study comprised 72 patients with calcium oxalate urolithiasis (study group) and 189 healthy adults from the general Russian population (control group). The study group consisted of 39 (54.2%) men and 33 (45.8%) women. The mean age of urolithiasis patients was 41.5+/-12...
July 2017: Urologii︠a︡
https://www.readbyqxmd.com/read/28803243/lithium-sensitivity-of-store-operated-ca2-entry-and-survival-of-fibroblasts-isolated-from-chorea-acanthocytosis-patients
#20
Lisann Pelzl, Bhaeldin Elsir, Itishri Sahu, Rosi Bissinger, Yogesh Singh, Basma Sukkar, Sabina Honisch, Ludger Schoels, Mohamed Jemaà, Elisabeth Lang, Alexander Storch, Andreas Hermann, Christos Stournaras, Florian Lang
BACKGROUND: The widely expressed protein chorein fosters activation of the phosphoinositide 3 kinase (PI3K) pathway thus supporting cell survival. Loss of function mutations of the chorein encoding gene VPS13A (vacuolar protein sorting-associated protein 13A) causes chorea-acanthocytosis (ChAc), a neurodegenerative disorder paralleled by deformations of erythrocytes. In mice, genetic knockout of chorein leads to enhanced neuronal apoptosis. PI3K dependent signalling upregulates Orai1, a pore forming channel protein accomplishing store operated Ca2+ entry (SOCE)...
August 11, 2017: Cellular Physiology and Biochemistry
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