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C Zhao, A Y-H Wu, X Yu, Y Gu, Y Lu, X Song, N An, Y Zhang
Airway remodeling manifested by hyperplasia of airway smooth muscle cells (ASMCs) and other structural and functional changes is a pathological condition in asthma not addressed by current treatment. Ca2+ signaling is crucial for ASMC proliferation. Inositol-1,4,5-trisphosphate receptor (IP3R) and ryanodine receptor (RyR) mediate Ca2+ release from endoplasmic reticulum/sarcoplasmic reticulum (ER/SR). Upon sensing the depletion of Ca2+ in ER/SR, stromal interaction molecule 1 (STIM1) aggregates and redistributes at the microdomain of ER/SR-plasma membrane (PM) and activates Orai1, a component of the store-operated Ca2+ (SOC) channels, to initiate Ca2+ influx...
April 2018: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
Tzu-Yu Huang, Yi-Hsin Lin, Heng-Ai Chang, Tzu-Ying Yeh, Ya-Han Chang, Yi-Fan Chen, Ying-Chi Chen, Chun-Chun Li, Wen-Tai Chiu
Platelet-derived growth factor (PDGF) has mitogenic and chemotactic effects on fibroblasts. An increase in intracellular Ca2+ is one of the first events that occurs following the stimulation of PDGF receptors (PDGFRs). PDGF activates Ca2+ elevation by activating the phospholipase C gamma (PLCγ)-signaling pathway, resulting in ER Ca2+ release. Store-operated Ca2+ entry (SOCE) is the major form of extracellular Ca2+ influx following depletion of ER Ca2+ stores and stromal interaction molecule 1 (STIM1) is a key molecule in the regulation of SOCE...
June 18, 2018: International Journal of Molecular Sciences
Hélène Cabanas, Thomas Harnois, Christophe Magaud, Laëtitia Cousin, Bruno Constantin, Nicolas Bourmeyster, Nadine Déliot
Background: Chronic myeloid leukemia (CML) results from hematopoietic stem cell transformation by the bcr-abl chimeric oncogene, encoding a 210 kDa protein with constitutive tyrosine kinase activity. In spite of the efficiency of tyrosine kinase inhibitors (TKI; Imatinib), other strategies are explored to eliminate CML leukemia stem cells, such as calcium pathways. Results: In this work, we showed that Store-Operated Calcium Entry (SOCE) and thrombin induced calcium influx were decreased in Bcr-Abl expressing 32d cells (32d-p210)...
May 29, 2018: Oncotarget
Chung-Hyun Cho, Keon Jin Lee, Eun Hui Lee
Skeletal muscle contracts or relaxes to maintain the body position and locomotion. For the contraction and relaxation of skeletal muscle, Ca2+ in the cytosol of skeletal muscle fibers acts as a switch to turn on and off a series of contractile proteins. The cytosolic Ca2+ level in skeletal muscle fibers is governed mainly by movement of Ca2+ between the cytosol and the sarcoplasmic reticulum (SR). Store-operated Ca2+ entry (SOCE), a Ca2+ entryway from the extracellular space to the cytosol, has gained a significant amount of attention from muscle physiologists...
June 14, 2018: BMB Reports
Haifeng Zheng, Bernard T Drumm, Scott Earley, Tae Sik Sung, Sang Don Koh, Kenton M Sanders
Electrical pacemaker activity generates phasic contractions and motility patterns such as segmentation and peristalsis in the gastrointestinal tract. Pacemaker currents are generated in interstitial cells of Cajal (ICC), which release Ca2+ from intracellular stores that stimulates Ca2+ -activated Cl- channels (CaCCs) in the plasma membrane. Thus, Ca2+ stores must be maintained to sustain pacemaker activity. Store-operated Ca2+ entry (SOCE) facilitates the refilling of Ca2+ stores by a mechanism dependent upon interactions between STIM and Orai proteins...
June 12, 2018: Science Signaling
Duaa Babaer, Suneetha Amara, Michael Ivy, Yan Zhao, Philip E Lammers, Jens M Titze, Venkataswarup Tiriveedhi
Recent evidence from our laboratory has demonstrated that high salt (Δ0.05 M NaCl) induced inflammatory response and cancer cell proliferation through salt inducible kinase-3 (SIK3) upregulation. As calcium influx is known to effect inflammatory response and drug resistance, we examined the impact of high salt on calcium influx in breast cancer cells. Treatment of MCF-7 and MDA-MB-231 cells with high salt induced an enhanced intracellular calcium intensity, which was significantly decreased by store operated calcium entry (SOCE) inhibitor co-treatment...
May 18, 2018: Oncotarget
Fengdan Dai, Yan Zhang, Qiang Wang, De Li, Yongjian Yang, Shuangtao Ma, Dachun Yang
BACKGROUND/AIMS: Activation of stromal interaction molecule 1 (STIM1) and Orai1 participates in the development of cardiac hypertrophy. Store-operated Ca2+ entry-associated regulatory factor (SARAF) is an intrinsic inhibitor of STIM1-Orai1 interaction. Thus, we hypothesized that SARAF could prevent cardiac hypertrophy. METHODS: Male C57BL/6 mice, aged 8 weeks, were randomly divided into sham and abdominal aortic constriction surgery groups and were infected with lentiviruses expressing SARAF and GFP (Lenti-SARAF) or GFP alone (Lenti-GFP) via intramyocardial injection...
May 22, 2018: Cellular Physiology and Biochemistry
Florian Lang, Lisann Pelzl, Stefan Hauser, Andreas Hermann, Christos Stournaras, Ludger Schöls
The pore forming Ca2+ release activated Ca2+ channel (CRAC) isoforms ORAI1-3 and their regulators STIM1,2 accomplish store operated Ca2+ entry (SOCE). Activation of SOCE may lead to cytosolic Ca2+ oscillations, which in turn support cell proliferation and cell survival. ORAI/STIM and thus SOCE are upregulated by the serum and glucocorticoid inducible kinase SGK1, a kinase under powerful genomic regulation and activated by phosphorylation via the phosphoinositol-3-phosphate pathway. SGK1 enhances ORAI1 abundance partially by phosphorylation of Nedd4-2, an ubiquitin ligase priming the channel protein for degradation...
May 3, 2018: Cell Calcium
Dong Yang, Xiaoyu Dai, Keqiang Li, Yangyang Xie, Jianpei Zhao, Mingjun Dong, Hua Yu, Zhenfang Kong
Stromal interaction molecule 1 (STIM1) is an endoplasmic reticulum Ca2+ sensor which has been reported to be overexpressed in numerous types of cancer, and is involved in the cell proliferation, invasion, migration and metastasis frequently observed in cancer. However, the role of STIM1 in colorectal cancer (CRC) remains unknown. The purpose of the present study was to investigate the effect of STIM1 in human CRC. The expression of STIM1 was specifically knocked down using lentivirus-mediated small hairpin RNA (shRNA) interference techniques in the CRC cell lines HCT116 and SW1116...
June 2018: Oncology Letters
Ka Cheung Tam, Eunus Ali, Jin Hua, Tim Chataway, Greg J Barritt
Ca2+ entry through store-operated Ca2+ channels (SOCs) in the plasma membrane (PM) of hepatocytes plays a central role in the hormonal regulation of liver metabolism. SOCs are composed of Orai1, the channel pore protein, and STIM1, the activator protein, and are regulated by hormones and reactive oxygen species (ROS). In addition to Orai1, STIM1 also interacts with several other intracellular proteins. Most previous studies of the cellular functions of Orai1 and STIM1 have employed immortalised cells in culture expressing ectopic proteins tagged with a fluorescent polypeptide such as GFP...
May 15, 2018: Cell Calcium
K K Petersen, C D Mørch, D Ligato, L Arendt-Nielsen
BACKGROUND: Offset analgesia (OA) is a disproportionally large decrease in the pain perception in response to a small decrease in the stimulation intensity. Traditionally, heat stimulation has been used to evoke OA. The aim of this study was to investigate if OA could be evoked by electrical stimulation. METHODS: Healthy volunteers (N=24) underwent two OA experimental sessions consisting of heat stimuli intensities of 48-49-48°C (traditional OA-paradigm) and electrical stimuli at 150-180-150% of the electrical pain perception (EPP) threshold...
May 24, 2018: European Journal of Pain: EJP
Sarita Rani Patnaik, Xun Zhang, Lincoln Biswas, Saeed Akhtar, Xinzhi Zhou, Deva Krupakar Kusuluri, James Reilly, Helen May-Simera, Susan Chalmers, John G McCarron, Xinhua Shu
Ciliopathies are a group of genetically heterogeneous disorders, characterized by defects in cilia genesis or maintenance. Mutations in the RPGR gene and its interacting partners, RPGRIP1 and RPGRIP1L , cause ciliopathies, but the function of their proteins remains unclear. Here we show that knockdown (KD) of RPGR, RPGRIP1 or RPGRIP1L in hTERT-RPE1 cells results in abnormal actin cytoskeleton organization. The actin cytoskeleton rearrangement is regulated by the small GTPase RhoA via the planar cell polarity (PCP) pathway...
May 1, 2018: Oncotarget
Heather A Nelson, Colin A Leech, Richard F Kopp, Michael W Roe
Store-operated calcium entry (SOCE), a fundamentally important homeostatic and Ca2+ signaling pathway in many types of cells, is activated by the direct interaction of stromal interaction molecule 1 (STIM1), an endoplasmic reticulum (ER) Ca2+ -binding protein, with Ca2+ -selective Orai1 channels localized in the plasma membrane. While much is known about the regulation of SOCE by STIM1, the role of stromal interaction molecule 2 (STIM2) in SOCE remains incompletely understood. Here, using clustered regularly interspaced short palindromic repeats -CRISPR associated protein 9 (CRISPR-Cas9) genomic editing and molecular imaging, we investigated the function of STIM2 in NIH 3T3 fibroblast and αT3 cell SOCE...
May 19, 2018: International Journal of Molecular Sciences
In-Sook Jeon, Hye-Ryun Kim, Eun-Young Shin, Eung-Gook Kim, Heon-Seok Han, Jin-Tae Hong, Hak-Kyo Lee, Ki-Duk Song, Joong-Kook Choi
Calcium mobilization is necessary for cell movement during embryonic development, lymphocyte synapse formation, wound healing, and cancer cell metastasis. Depletion of calcium in the lumen of the endoplasmic reticulum using inositol triphosphate (IP3) or thapsigargin (TG) is known to induce oligomerization and cytoskeleton-mediated translocation of stromal interaction molecule 1 (STIM1) to the plasma membrane, where it interacts with the calcium release-activated calcium channel Orai1 to mediate calcium influx; this process is referred to as store-operated calcium entry (SOCE)...
May 21, 2018: Experimental & Molecular Medicine
Ralph J Stevenson, Iman Azimi, Jack U Flanagan, Marco Inserra, Irina Vetter, Gregory R Monteith, William A Denny
The proteins Orai1 and STIM1 control store-operated Ca2+ entry (SOCE) into cells. SOCE is important for migration, invasion and metastasis of MDA-MB-231 human triple negative breast cancer (TNBC) cells and has been proposed as a target for cancer drug discovery. Two hit compounds from a medium throughput screen, displayed encouraging inhibition of SOCE in MDA-MB-231 cells, as measured by a Fluorescence Imaging Plate Reader (FLIPR) Ca2+ assay. Following NMR spectroscopic analysis of these hits and reassignment of their structures as 5-hydroxy-5-trifluoromethylpyrazolines, a series of analogues was prepared via thermal condensation reactions between substituted acylhydrazones and trifluoromethyl 1,3-dicarbonyl arenes...
May 9, 2018: Bioorganic & Medicinal Chemistry
J Ye, J Xie
Objective: To study the effects of stromal interaction molecule 1 (STIM1) RNA interference on cell proliferation, apoptosis, invasion and migration ability in vitro in human laryngeal cancer cells Hep-2. Method: Lentivirus transfection was used to realize the STIM1 RNA interference in human laryngeal cancer cells Hep-2. STIM1 RNA interference was verified by real-time PCR and western blotting. The cell proliferation was analyzed by CCK-8 method, Transwell chamber and wound scratch assay were used to detect cell invasion and migration ability, respectively...
June 5, 2017: Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery
Qiao-Chu Wang, Xi Wang, Tie-Shan Tang
STIM1 activates store-operated Ca2+ entry when Ca2+ in the endoplasmic reticulum (ER) is depleted. In this issue, Chang et al. (2018. J. Cell Biol. demonstrate that EB1 traps STIM1 at dynamic contacts between the ER and microtubule plus ends, delaying STIM1 translocation to ER-plasma membrane junctions and preventing Ca2+ overload.
May 15, 2018: Journal of Cell Biology
Priscilla S-W Yeung, Megumi Yamashita, Christopher E Ing, Régis Pomès, Douglas M Freymann, Murali Prakriya
Store-operated Orai1 channels are activated through a unique inside-out mechanism involving binding of the endoplasmic reticulum Ca2+ sensor STIM1 to cytoplasmic sites on Orai1. Although atomic-level details of Orai structure, including the pore and putative ligand binding domains, are resolved, how the gating signal is communicated to the pore and opens the gate is unknown. To address this issue, we used scanning mutagenesis to identify 15 residues in transmembrane domains (TMs) 1-4 whose perturbation activates Orai1 channels independently of STIM1...
May 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
Cristina Pierro, Xuexin Zhang, Cynthia Kankeu, Mohamed Trebak, Martin D Bootman, H Llewelyn Roderick
The KRAS GTPase plays a fundamental role in transducing signals from plasma membrane growth factor receptors to downstream signalling pathways controlling cell proliferation, survival and migration. Activating KRAS mutations are found in 20% of all cancers and in up to 40% of colorectal cancers, where they contribute to dysregulation of cell processes underlying oncogenic transformation. Multiple KRAS-regulated cell functions are also influenced by changes in intracellular Ca2+ levels that are concurrently modified by receptor signalling pathways...
June 2018: Cell Calcium
Kuo-Hao Ho, Cheng-Kuei Chang, Peng-Hsu Chen, Yu-Jia Wang, Wei-Chiao Chang, Ku-Chung Chen
Glioblastoma multiforme (GBM) is the most common brain tumor in adults. Due to its highly invasive nature, it is not easy to treat, resulting in high mortality rates. Stromal interacting molecule 1 (Stim1) plays important roles in regulating store-operated Ca2+ entry (SOCE), and controls invasion by cancer cells. However, the mechanisms and functions of Stim1 in glioma progression are still unclear. In this study, we investigated the effects of targeting Stim1 expression on glioma cell invasion. By analyzing profiles of GBM patients from RNA-sequencing data in The Cancer Genome Atlas (TCGA), higher expression levels of STIM1 were correlated with the poor survival...
May 10, 2018: Journal of Neurochemistry
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