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Sen Yang, Dongwen Wang, Xiaoming Cao, Xuhui Zhang, Xiaobin Yuan, Tiancheng Yang, Yang Mi
Store operated calcium channels (SOCCs) have been suggested to play a critical role in many diabetic complications. Diabetic cystopathy (DCP) is common in patients with diabetes, but the role of SOCCs in DCP is still unclear. The aim of the present study was to investigate the role of SOCCs in DCP with streptozocin (STZ)‑induced diabetic rats. Specifically, the authors investigated whether SOCCs were altered in streptozocin (STZ)‑induced diabetic rats and, if so, how this may contribute to the contraction of bladder detrusor strips and the intracellular Ca2+ concentration of bladder smooth muscle cells in diabetic rats...
March 9, 2018: Molecular Medicine Reports
Wen-Tai Chiu, Heng-Ai Chang, Yi-Hsin Lin, Yu-Shan Lin, Hsiao-Tzu Chang, Hsi-Hui Lin, Soon-Cen Huang, Ming-Jer Tang, Meng-Ru Shen
Ca2+ plays a significant role in linking the induction of apoptosis. The key anti-apoptotic protein, Bcl-2, has been reported to regulate the movement of Ca2+ across the ER membrane, but the exact effect of Bcl-2 on Ca2+ levels remains controversial. Store-operated Ca2+ entry (SOCE), a major mode of Ca2+ uptake in non-excitable cells, is activated by depletion of Ca2+ in the ER. Depletion of Ca2+ in the ER causes translocation of the SOC channel activator, STIM1, to the plasma membrane. Thereafter, STIM1 binds to Orai1 or/and TRPC1 channels, forcing them to open and thereby allow Ca2+ entry...
December 2018: Cell Death Discovery
Mickaël F El Hachmane, Charlotta S Olofsson
Ca2+ impacts a large array of cellular processes in every known cell type. In the white adipocyte, Ca2+ is involved in regulation of metabolic processes such as lipolysis, glucose uptake and hormone secretion. Although the importance of Ca2+ in control of white adipocyte function is clear, knowledge is still lacking regarding the control of dynamic Ca2+ alterations within adipocytes and mechanisms inducing intracellular Ca2+ changes remain elusive. Own work has recently demonstrated the existence of store-operated Ca2+ entry (SOCE) in lipid filled adipocytes...
March 7, 2018: Biochemical and Biophysical Research Communications
Priyodarshan Goswamee, Tamar Pounardjian, David R Giovannucci
Background: Store-operated Ca2+ entry (SOCE) has been implicated in the migration of some cancer cell lines. The canonical SOCE is defined as the Ca2+ entry that occurs in response to near-maximal depletion of Ca2+ within the endoplasmic reticulum. Alternatively, arachidonic acid (AA) has been shown to induce Ca2+ entry in a store-independent manner through Orai1/Orai3 hetero-multimeric channels. However, the role of this AA-induced Ca2+ entry pathway in cancer cell migration has not been adequately assessed...
2018: Cancer Cell International
Hang Cao, Anja T Umbach, Rosi Bissinger, Meinrad Gawaz, Florian Lang
BACKGROUND/AIMS: The anaplastic lymphoma (tyrosine) kinase (ALK) inhibitor ceritinib triggers apoptosis of tumor cells and eryptosis of erythrocytes. Blood platelets may similarly enter a state resembling apoptosis, which could be triggered by activation with collagen related peptide (CRP). CRP-induced platelet apoptosis is characterized by cell membrane scrambling with phosphatidylserine exposure to the platelet surface and cell shrinkage, preceded by externalization of Ca2+ channel Orai1, increase of cytosolic Ca2+-activity ([Ca2+]i), formation of reactive oxygen species (ROS), and caspase activation...
February 23, 2018: Cellular Physiology and Biochemistry
Marc Fahrner, Michael Stadlbauer, Martin Muik, Petr Rathner, Peter Stathopulos, Mitsu Ikura, Norbert Müller, Christoph Romanin
STIM1 and Orai1 are key components of the Ca2+ -release activated Ca2+ (CRAC) current. Orai1, which represents the subunit forming the CRAC channel complex, is activated by the ER resident Ca2+ sensor STIM1. The genetically inherited Stormorken syndrome disease has been associated with the STIM1 single point R304W mutant. The resulting constitutive activation of Orai1 mainly involves the CRAC-activating domain CAD/SOAR of STIM1, the exposure of which is regulated by the molecular interplay between three cytosolic STIM1 coiled-coil (CC) domains...
February 26, 2018: Nature Communications
Jun Wu, Daniel Ryskamp, Lutz Birnbaumer, Ilya Bezprozvanny
BACKGROUND: Huntington disease (HD) is a dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. We previously discovered that mutant Huntingtin sensitizes type 1 inositol 1,4,5-trisphosphate receptor (InsP3R1) to InsP3. This causes calcium leakage from the endoplasmic reticulum (ER) and a compensatory increase in neuronal store-operated calcium (nSOC) entry. We previously demonstrated that supranormal nSOC leads to synaptic loss in striatal medium spiny neurons (MSNs) in YAC128 HD mice...
2018: Journal of Huntington's Disease
Shuhua Zheng, Gilles M Leclerc, Bin Li, Ronan T Swords, Julio C Barredo
De novo and acquired drug resistance and subsequent relapse remain major challenges in acute lymphoblastic leukemia (ALL). We previously identified that pevonedistat (TAK-924, MLN4924), a first-in-class inhibitor of NEDD8 activating enzyme (NAE), elicits ER stress and has potent in vitro and in vivo efficacy against ALL. However, in pevonedistat-treated ALL cell lines, we found consistent activation of the pro-survival MEK/ERK pathway, which has been associated with relapse and poor outcome in ALL. We uncovered that inhibition of the MEK/ERK pathway in vitro and in vivo sensitized ALL cells to pevonedistat...
January 19, 2018: Oncotarget
Wei Zhang, Terunao Takahara, Takuya Achiha, Hideki Shibata, Masatoshi Maki
NFAT is a cytoplasm-localized hyper-phosphorylated transcription factor that is activated through dephosphorylation by calcineurin, a Ca2+ /calmodulin-dependent phosphatase. A non-palindromic NFAT-response element (RE) found in the IL2 promoter region has been commonly used for a Ca2+ -response reporter gene system, but requirement of concomitant activation of AP-1 (Fos/Jun) often complicates the interpretation of obtained results. A new nanoluciferase (NanoLuc) reporter gene containing nine-tandem repeats of a pseudo-palindromic NFAT-RE located upstream of the IL8 promoter was designed to monitor Ca2+ -induced transactivation activity of NFAT in human embryonic kidney (HEK) 293 cells by measuring luciferase activities of NanoLuc and co-expressed firefly luciferase for normalization...
February 18, 2018: International Journal of Molecular Sciences
Olivier Gouin, Killian L'Herondelle, Paul Buscaglia, Christelle Le Gall-Ianotto, Réginald Philippe, Nelig Legoux, Olivier Mignen, Virginie Buhé, Raphael Leschiera, Mehdi Sakka, Nathalie Kerfant, Jean-Luc Carré, Raphaele Le Garrec, Luc Lefeuvre, Nicolas Lebonvallet, Laurent Misery
Proteinase-activated receptor-2 (PAR-2) activation in basal keratinocytes stimulates inflammation via the Ca2+ -dependent production of mediators such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α and thymic stromal lymphopoietin (TSLP). In this study, we investigated PAR-2 calcium signaling and the consequent production of inflammatory mediators in differentiated human primary keratinocytes (DhPKs). Stimulation with the PAR-2 activating peptide SLIGKV promoted Ca2+ store depletion in both undifferentiated human primary keratinocytes (UhPKs) and DhPKs...
February 16, 2018: Journal of Investigative Dermatology
Nguyen Thi Xuan, Nong Van Hai
Klotho (KL) encodes a single-pass transmembrane protein and is predominantly expressed in the kidney, parathyroid glands, and choroid plexus. Genetic studies on the KL gene have revealed that DNA hypermethylation is one of the major risk factors for aging, diseases, and cancer. Besides, KL exerts anti-inflammatory and anti-tumor effects by regulating signaling pathways and the expression of target genes. KL participates in modulation of the insulin/insulin-like growth factor-1 (IGF-1) signaling, which induces the growth hormone (GH) secretion...
January 2018: Iranian Journal of Basic Medical Sciences
Xiao Zhou, Kim S Friedmann, Hélène Lyrmann, Yan Zhou, Rouven Schoppmeyer, Arne Knörck, Sebastian Mang, Cora Hoxha, Adrian Angenendt, Christian S Backes, Carmen Mangerich, Renping Zhao, Sabrina Cappello, Gertrud Schwär, Carmen Hässig, Marc Neef, Bernd Bufe, Frank Zufall, Karsten Kruse, Barbara A Niemeyer, Annette Lis, Bin Qu, Carsten Kummerow, Eva C Schwarz, Markus Hoth
Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells are required to protect the human body against cancer. Ca2+ is a key metabolic factor for lymphocyte function and cancer homeostasis. We analysed the Ca2+ dependence of CTL and NK cell cytotoxicity against cancer cells and found that CTL have a bell-shaped Ca2+ dependence with an optimum for cancer cell elimination at rather low [Ca2+ ]ext (23-630 μm) and [Ca2+ ]int (122-334 nm). This finding predicts that a partial inhibition of Orai1 should increase (rather than decrease) cytotoxicity of CTL at [Ca2+ ]ext higher than 630 μm...
January 25, 2018: Journal of Physiology
Lu Zhang, Chi-Hong Chao, Laurie A Jaeger, Agnes Bali Papp, Zoltan Machaty
The Ca2+ entry mechanism that sustains the Ca2+ oscillations in fertilized pig oocytes was investigated. STIM1 and ORAI1 proteins tagged with various fluorophores were expressed in the oocytes. In some cells, the Ca2+ stores were depleted using cyclopiazonic acid (CPA); others were inseminated. Changes in the oocytes' cytosolic free Ca2+ concentration were monitored, while interaction between the expressed fusion proteins was investigated using fluorescence resonance energy transfer (FRET). Store depletion led to an increase of the FRET signal in oocytes co-expressing mVenus-STIM1 and mTurquoise2-ORAI1, indicating that Ca2+ release was followed by an interaction between these proteins...
January 22, 2018: Biology of Reproduction
Hui Jiang, Shubiao Zou, Sarika Chaudhari, Rong Ma
The short-term effect of high glucose (HG) treatment on store-operated Ca2+ entry in mesangial cells (MCs) is not well known. The aim of the present study was to determine whether and how HG treatment for a short period altered protein abundance of Orai1, the channel mediating store-operated Ca2+ entry in MCs. Rat and human MCs were exposed to HG (25 mM) for 2, 4, 8, and 24 hours and the abundance of Orai1 protein was significantly decreased at the time point of 8 and 16 hours. Consistently, HG treatment for 8 hours significantly reduced store-operated Ca2+ entry in rat MCs...
January 24, 2018: American Journal of Physiology. Renal Physiology
Florence Domenichini, Elodie Terrié, Patricia Arnault, Thomas Harnois, Christophe Magaud, Patrick Bois, Bruno Constantin, Valérie Coronas
The subventricular zone (SVZ) is the major stem cell niche in the brain of adult mammals. Within this region, neural stem cells proliferate, self-renew and give birth to neurons and glial cells. Previous studies underlined enrichment in calcium signaling-related transcripts in adult neural stem cells. Because of their ability to mobilize sustained calcium influxes in response to a wide range of extracellular factors, store-operated channels (SOC) appear to be, among calcium channels, relevant candidates to induce calcium signaling in neural stem cells whose cellular activities are continuously adapted to physiological signals from the microenvironment...
January 23, 2018: Stem Cells
Zhen-Dong Zhu, Tao Yu, Hua-Jing Liu, Jing Jin, Jun He
Acute pancreatitis (AP) is an acute inflammatory process of the pancreas that is characterized by inflammation, edema, vacuolization and necrosis, which has significant morbidity and lethality. The pathogenesis of AP has not been established completely. An early and critical feature of AP is the aberrant signaling of Calcium (Ca2+) within the pancreatic acinar cell, termed Ca2+ overload. Store-operated Ca2+ (SOC) channels are the principal Ca2+ influx channels that contribute to Ca2+ overload in pancreatic acinar cells...
January 19, 2018: Cell Death & Disease
Xi He, Shanshan Song, Ramon J Ayon, Angela Balisterieri, Stephen M Black, Ayako Makino, W Gil Wier, Wei-Jin Zang, Jason X-J Yuan
Ca2+ signaling, particularly the mechanism via store-operated Ca2+ entry (SOCE) and receptor-operated Ca2+ entry (ROCE), plays a critical role in the development of acute hypoxia-induced pulmonary vasoconstriction and chronic hypoxia-induced pulmonary hypertension. This study aimed to test the hypothesis that chronic hypoxia differentially regulates the expression of proteins that mediate SOCE and ROCE (STIM, Orai, and TRPC6) in pulmonary (PASMC) and coronary (CASMC) artery smooth muscle cells. The resting cytosolic [Ca2+] ([Ca2+]cyt) and the stored [Ca2+] in the sarcoplasmic reticulum (SR) were not different in CASMC and PASMC...
January 3, 2018: American Journal of Physiology. Cell Physiology
Lakshmi Maganti, Sutapa Dutta, Mahua Ghosh, J Chakrabarti
Here we study microscopic mechanism of complex formation between Ca2+ bound -calmodulin (holoCaM) and Orai1 that regulates Ca2+-dependent inactivation process in eukaryotic cells. We compute conformational thermodynamic changes in holoCaM with respect to complex of Orai1 bound to C-terminal domain of holoCaM using histograms of dihedral angles of the proteins over trajectories from molecular dynamics simulations. Our analysis shows that the N-terminal domain residues L4, T5, Q41, N42, T44 and E67 of holoCaM get destabilized and disordered due to Orai1 binding to C-terminal domain of calmodulin affect the N-terminal domain residues...
January 18, 2018: Journal of Biomolecular Structure & Dynamics
Jie-Bin Zhou, Ying-Ying Sun, Ying-Lin Zheng, Chu-Qin Yu, Hua-Qing Lin, Ji-Yan Pang
In this study, the effect of four xyloketals 1-4 on store-operated calcium entry (SOCE) was investigated in primary distal pulmonary arterial smooth muscle cells (PASMCs) isolated from mice. The results showed that xyloketal A (1), an unusual ketal with C-3 symmetry, exhibited strong SOCE blocking activity. Secretion of interleukin-8 (IL-8) was also inhibited by xyloketal A. The parallel artificial membrane permeability assay (PAMPA) of 1-4 suggested that these xyloketals penetrated easily through the cell membrane...
December 20, 2017: Acta Pharmaceutica
Mickaël F El Hachmane, Anna Ermund, Cecilia Brännmark, Charlotta S Olofsson
Here we have applied ratiometric measurements of intracellular Ca2+ concentrations ([Ca2+]i) to show that extracellularly applied ATP (100 mM) stimulates store-operated Ca2+ entry (SOCE) in 3T3-L1 adipocytes. ATP produced a rapid increase in [Ca2+]i consisting of an initial transient elevation followed by a sustained elevated phase that could be observed only in the presence of extracellular Ca2+ Gene expression data and [Ca2+]i recordings with uridine-5'-triphosphate (UTP) or with the phospholipase C (PLC) inhibitor U73122 demonstrated the involvement of purinergic P2Y2 receptors and the PLC/inositol trisphosphate (IP3) pathway...
January 15, 2018: Biochemical Journal
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