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https://www.readbyqxmd.com/read/29131377/new-insights-of-subfertility-among-transplanted-women-immunosuppressive-drug-fk506-leads-to-calcium-leak-and-oocyte-activation-before-fertilization
#1
Linlin Liu, Man Yang, Naiqiang Wang, Li Li, Zi-Jiang Chen, Cong Zhang
FKBP12, known as FK506 binding protein, binds to immunosuppressive drug FK506, which must be taken by patients who received organ transplant. The side effect of FK506 is that women have difficulties in bearing a baby, so it is important to find the reason of their subfertility. This research explored the expression of FKBP12 in pre-implantation embryos and investigated its potential effect on reproduction. The results demonstrate that FKBP12 had good co-localization with endoplasmic reticulum and inositol-1, 4, 5- trisphosphate receptor in pre-implantation stages...
November 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29129580/the-%C3%AE-and-%C3%AE-2%C3%AE-auxiliary-subunits-of-cav1-channels-are-required-for-th2-lymphocyte-function-and-acute-allergic-airway-inflammation
#2
Nicolas Rosa, Emily Triffaux, Virginie Robert, Marion Mars, Martin Klein, Gregory Bouchaud, Astrid Canivet, Antoine Magnan, Jean-Charles Guéry, Lucette Pelletier, Magali Savignac
BACKGROUND: T-lymphocytes express not only the cell membrane calcium ORAI1 but also voltage-dependent Cav1 channels. In excitable cells, these channels are composed of the ion forming pore α1 and auxiliary subunits (β and α2δ) needed for proper trafficking and activation of the channel. We previously disclosed the role of Cav1.2 α1 in mouse and human Th2- but not Th1-cell functions and showed that knocking-down Cav1 α1 prevents experimental asthma OBJECTIVE: We investigated the role of β and α2δ auxiliary subunits on Cav1 α1 function in Th2 lymphocytes and on the development of acute allergic airway inflammation...
November 9, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29129205/the-steroid-hormone-20-hydroxyecdysone-upregulates-calcium-release-activated-calcium-channel-modulator-1-expression-to-induce-apoptosis-in-the-midgut-of-helicoverpa-armigera
#3
Yong-Bo Li, Xu-Yang Pei, Di Wang, Cai-Hua Chen, Mei-Juan Cai, Jin-Xing Wang, Xiao-Fan Zhao
Animal steroid hormones stimulate extracellular Ca(2+) influx into cells; however, the mechanism remains unclear. In this study, we determined that the Ca(2+) influx induced by steroid hormone 20-hydroxyecdysone (20E) is mediated by the calcium release-activated calcium channel modulator 1 (CRACM1/Orai1). The Orai1 mRNA is highly expressed during midgut programmed cell death in the lepidopteran insect Helicoverpa armigera. 20E upregulated the expression of Orai1 in H. armigera larvae and in an epidermal cell line (HaEpi)...
December 2017: Cell Calcium
https://www.readbyqxmd.com/read/29109429/knockdown-of-amyloid-precursor-protein-increases-calcium-levels-in-the-endoplasmic-reticulum
#4
Kinga Gazda, Jacek Kuznicki, Tomasz Wegierski
Familial Alzheimer's disease (AD) is caused by mutations in the genes that encode amyloid precursor protein (APP) and presenilins. Disturbances in calcium homeostasis have been observed in various cellular and animal models of AD and are proposed to underlie the pathogenesis of the disease. Furthermore, wildtype presenilins were shown to regulate endoplasmic reticulum (ER) calcium homeostasis, although their precise mechanism of action remains controversial. To investigate whether APP also affects ER calcium levels, we used RNA interference to target the APP gene in cultured T84 cells in combination with two types of ER calcium sensors...
November 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29101179/reduced-membrane-cholesterol-following-chronic-hypoxia-limits-orai1-mediated-pulmonary-endothelial-ca-2-entry
#5
Bojun Zhang, Jay S Naik, Nikki L Jernigan, Benjimen R Walker, Thomas C Resta
Endothelial dysfunction in chronic hypoxia (CH)-induced pulmonary hypertension is characterized by reduced store-operated Ca(2+) entry (SOCE) and diminished Ca(2+)-dependent production of endothelium-derived vasodilators. We recently reported that SOCE in pulmonary arterial endothelial cells (PAEC) is tightly regulated by membrane cholesterol, and that decreased membrane cholesterol is responsible for impaired SOCE following CH. However, the ion channels involved in cholesterol-sensitive SOCE are unknown. We hypothesized that cholesterol facilitates SOCE in PAEC through the interaction of Orai1 and stromal interaction molecule 1 (STIM1)...
November 3, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29089467/suppression-of-stim1-reduced-intracellular-calcium-concentration-and-attenuated-hypoxia-reoxygenation-induced-apoptosis-in-h9c2-cells
#6
Fei He, Qianfu Wu, Banglong Xu, Xiaocheng Wang, Jixiong Wu, Li Huang, Jing Cheng
Objective: Previous studies have demonstrated STIM1-mediated store-operated Ca(2+) entry(SOCE) contributes to intracellular Ca(2+) accumulation. The present study aimed to investigate the expression of STIM1 and Orai1/TRPC1 in the context of myocardial ischemia/reperfusion injury(MIRI) and the effect of STIM1 inhibition on Ca(2+) accumulation and apoptosis in H9c2 cardiomyocytes subjected to hypoxia/reoxygenation(H/R). Methods: Expression of STIM1/Orai1/TRPC1 was determined by RT-PCR and Western Blot in mice subjected to MIRI and H9C2 cardiomyocytes subjected to H/R...
October 31, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29079778/exercise-dependent-formation-of-new-junctions-that-promote-stim1-orai1-assembly-in-skeletal-muscle
#7
Simona Boncompagni, Antonio Michelucci, Laura Pietrangelo, Robert T Dirksen, Feliciano Protasi
Store-operated Ca(2+) entry (SOCE), a ubiquitous mechanism that allows recovery of Ca(2+) ions from the extracellular space, has been proposed to limit fatigue during repetitive skeletal muscle activity. However, the subcellular location for SOCE in muscle fibers has not been unequivocally identified. Here we show that exercise drives a significant remodeling of the sarcotubular system to form previously unidentified junctions between the sarcoplasmic reticulum (SR) and transverse-tubules (TTs). We also demonstrate that these new SR-TT junctions contain the molecular machinery that mediate SOCE: stromal interaction molecule-1 (STIM1), which functions as the SR Ca(2+) sensor, and Orai1, the Ca(2+)-permeable channel in the TT...
October 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29073606/inhibitory-effect-of-afatinib-on-platelet-activation-and-apoptosis
#8
Hang Cao, Abdulla Al Mamun Bhuyan, Anja T Umbach, Rosi Bissinger, Meinrad Gawaz, Florian Lang
BACKGROUND/AIMS: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor afatinib is used for the treatment of several malignancies. Afatinib is at least partially effective by triggering apoptosis of tumor cells. Platelets may similarly undergo apoptosis, which is characterized by caspase 3 activation, cell shrinkage and phosphatidylserine translocation. However, an effect of afatinib on platelets has never been reported. The present study explored whether treatment of platelets with afatinib modifies platelet activation and apoptosis in the absence and presence of platelet activators thrombin or collagen related peptide (CRP)...
October 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29053813/comparative-transcriptomic-analysis-of-high-and-low-egg-producing-duck-ovaries
#9
Z Tao, W Song, C Zhu, W Xu, H Liu, S Zhang, Li Huifang
The egg-laying rate is an important indicator of egg production of laying ducks. Egg production directly impacts the economic benefits of the duck industry. In order to obtain better insight into the molecular mechanisms associated with the process of egg production, comparative transcriptomic analysis of the ovaries of Jinding ducks with high and low egg production was performed using the Illumina HiSeq 2500 system. A total of 843 differentially expressed genes (DEGs) was identified, 367 that were down-regulated and 476 that were up-regulated in high egg production (HEP) ovaries, as compared with low egg production (LEP) ovaries...
October 5, 2017: Poultry Science
https://www.readbyqxmd.com/read/29053695/targeting-cysteine-thiols-for-in-vitro-site-specific-glycosylation-of-recombinant-proteins
#10
Yoo Jung Choi, Jinhui Zhu, Steve Chung, Naveed Siddiqui, Qingping Feng, Peter B Stathopulos
Stromal interaction molecule-1 (STIM1) is a type-I transmembrane protein located on the endoplasmic reticulum (ER) and plasma membranes (PM). ER-resident STIM1 regulates the activity of PM Orai1 channels in a process known as store operated calcium (Ca(2+)) entry which is the principal Ca(2+) signaling process that drives the immune response. STIM1 undergoes post-translational N-glycosylation at two luminal Asn sites within the Ca(2+) sensing domain of the molecule. However, the biochemical, biophysical, and structure biological effects of N-glycosylated STIM1 were poorly understood until recently due to an inability to readily obtain high levels of homogeneous N-glycosylated protein...
October 4, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29051492/calmodulin-dissociates-the-stim1-orai1-complex-and-stim1-oligomers
#11
Xin Li, Guangyan Wu, Yin Yang, Shijuan Fu, Xiaofen Liu, Huimin Kang, Xue Yang, Xun-Cheng Su, Yuequan Shen
Store-operated calcium entry (SOCE) is a major pathway for calcium ions influx into cells and has a critical role in various cell functions. Here we demonstrate that calcium-bound calmodulin (Ca(2+)-CaM) binds to the core region of activated STIM1. This interaction facilitates slow Ca(2+)-dependent inactivation after Orai1 channel activation by wild-type STIM1 or a constitutively active STIM1 mutant. We define the CaM-binding site in STIM1, which is adjacent to the STIM1-Orai1 coupling region. The binding of Ca(2+)-CaM to activated STIM1 disrupts the STIM1-Orai1 complex and also disassembles STIM1 oligomer...
October 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/29038464/unveiling-some-fda-approved-drugs-as-inhibitors-of-the-store-operated-ca-2-entry-pathway
#12
Saifur Rahman, Taufiq Rahman
The store-operated calcium entry (SOCE) pathway is an important route for generating cytosolic Ca(2+) signals that regulate a diverse array of biological processes. Abnormal SOCE seem to underlie several diseases that notably include allergy, inflammation and cancer. Therefore, any modulator of this pathway is likely to have significant impact in cell biology under both normal and abnormal conditions. In this study, we screened the FDA-approved drug library for agents that share significant similarity in 3D shape and surface electrostatics with few, hitherto best known inhibitors of SOCE...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29029788/differential-ca-2-mobilization-and-mast-cell-degranulation-by-fc%C3%AE%C2%B5ri-and-gpcr-mediated-signaling
#13
Ying-Chi Chen, Yu-Chung Chang, Heng-Ai Chang, Yu-Shan Lin, Chiung-Wen Tsao, Meng-Ru Shen, Wen-Tai Chiu
Mast cells play a primary role in allergic diseases. During an allergic reaction, mast cell activation is initiated by cross-linking IgE-FcεRI complex by multivalent antigen resulting in degranulation. Additionally, G protein-coupled receptors also induce degranulation upon activation. However, the spatio-temporal relationship between Ca(2+) mobilization and mast cell degranulation is not well understood. We investigated the relationship between oscillations in Ca(2+) level and mast cell degranulation upon stimulation in rat RBL-2H3 cells...
November 2017: Cell Calcium
https://www.readbyqxmd.com/read/29024298/detailed-evidence-for-an-unparalleled-interaction-mode-between-calmodulin-and-orai-proteins
#14
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 is 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-molecular 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/28978262/molecular-dynamics-studies-on-conformational-thermodynamics-of-orai1-calmodulin-complex
#15
Lakshmi Maganti, Mahua Ghosh, J Chakrabarti
Molecular understanding of bio-macromolecular binding is a challenging task due to large sizes of the molecules and presence of variety of interactions. Here we study the molecular mechanism of calmodulin (CaM) binding to Orai1 that regulates Ca(2+)-dependent inactivation process in eukaryotic cells. Although experimental observations indicate that Orai1 binds to the C-terminal of Ca(2+) loaded CaM, it is not decisive if N-domain of CaM interacts with Orai1. We address the issue of interaction of different domains of CaM with Orai1 using conformational thermodynamic changes, computed from histograms of dihedral angles over simulated trajectories of CaM, CaM binding domain of Orai1 and complexes of CaM with Orai1...
October 5, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28972171/inhibition-of-the-sarco-endoplasmic-reticulum-er-ca2-atpase-by-thapsigargin-analogs-induces-cell-death-via-er-ca2-depletion-and-the-unfolded-protein-response
#16
Pankaj Sehgal, Paula Szalai, Claus Olesen, Helle A Praetorius, Poul Nissen, Søren Brøgger Christensen, Nikolai Engedal, Jesper Vuust Møller
Calcium (Ca2+) is a fundamental regulator of cell signaling and function. Thapsigargin (Tg) blocks the sarco/endoplasmic reticulum (ER) Ca2+-ATPase (SERCA), disrupts Ca2+ homeostasis, and causes cell death. However, the exact mechanisms whereby SERCA-inhibition induces cell death are incompletely understood. Here, we report that low (0.1 μM) concentrations of Tg and Tg analogs with various long-chain substitutions at the O(8) position extensively inhibit SERCA1a-mediated Ca2+ transport. We also found that in both prostate and breast cancer cells, exposure to Tg or Tg analogs for 1 day caused extensive drainage of the ER Ca2+ stores...
September 29, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28966111/cationic-liposomes-suppress-intracellular-calcium-ion-concentration-increase-via-inhibition-of-pi3-kinase-pathway-in-mast-cells
#17
Yoshikazu Inoh, Aki Haneda, Satoshi Tadokoro, Satoru Yokawa, Tadahide Furuno
Cationic liposomes are commonly used as vectors to effectively introduce foreign genes (antisense DNA, plasmid DNA, siRNA, etc.) into target cells. Cationic liposomes are also known to affect cellular immunocompetences such as the mast cell function in allergic reactions. In particular, we previously showed that the cationic liposomes bound to the mast cell surface suppress the degranulation induced by cross-linking of high affinity IgE receptors in a time- and dose-dependent manner. This suppression is mediated by impairment of the sustained level of intracellular Ca(2+) concentration ([Ca(2+)]i) via inhibition of store-operated Ca(2+) entry (SOCE)...
December 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28928244/selective-inhibitory-effects-of-zinc-on-cell-proliferation-in-esophageal-squamous-cell-carcinoma-through-orai1
#18
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
#19
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
#20
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...
December 2017: Biochimica et Biophysica Acta
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