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Camille D Dago, Paul Le Maux, Thierry Roisnel, Christophe Brigaudeau, Yves-Alain Bekro, Olivier Mignen, Jean-Pierre Bazureau
From a series of (1 R , 1 S )-1[β-(phenylalkoxy)-(phenetyl)]-1 H -pyrazolium hydrochloride as new analogues of SKF-96365, one has an interesting effect for endoplasmic reticulum (ER) Ca2+ release and store-operated Ca2+ entry (SOCE) (IC50 25 μM) on the PLP-B lymphocyte cell line. A successful resolution of (±) 1-phenyl-2-(1 H -pyrazol-1-yl)ethan-1-ol has been developed by using the method of "half-concentration" in the presence of (+)-(1 S )- or (-)-(1 R )-CSA.
March 14, 2018: International Journal of Molecular Sciences
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
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
Pavani Beesetty, Krystyna B Wieczerzak, Jennifer N Gibson, Taku Kaitsuka, Charles Tuan Luu, Masayuki Matsushita, J Ashot Kozak
T lymphocytes enlarge (blast) and proliferate in response to antigens in a multistep program that involves obligatory cytosolic calcium elevations. Store-operated calcium entry (SOCE) pathway is the primary source of Ca 2+ in these cells. Here, we describe a novel modulator of blastogenesis, proliferation and SOCE: the TRPM7 channel kinase. TRPM7 kinase-dead (KD) K1646R knock-in mice exhibited splenomegaly and impaired blastogenic responses elicited by PMA/ionomycin or anti-CD3/CD28 antibodies. Splenic T-cell proliferation in vitro was weaker in the mutant compared to wildtype littermates...
February 14, 2018: Scientific Reports
Davide Meani, Mladen Solarić, Harri Visapää, Rose-Marie Rosén, Robert Janknegt, Majana Soče
Background: Androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone (LHRH) agonists is well established for the treatment of men with metastatic prostate cancer. As clear differences in efficacy, safety, or tolerability between the available LHRH agonists are lacking, the healthcare management team needs to look to practical differences between the formulations when selecting therapy for their patients. Moreover, as the economic burden of prostate cancer rises alongside earlier diagnosis and improved survival, the possibility for cost savings by using products with specific features is growing in importance...
February 2018: Therapeutic Advances in Urology
Xin Yang, Guorong Wen, Biguang Tuo, Fenglian Zhang, Hanxing Wan, Jialin He, Shiming Yang, Hui Dong
Background and Purpose: Although Ca2+ signaling may stimulate small intestinal ion secretion, little is known about its critical role and the molecular mechanisms of Ca2+-mediated biological action. Key Results: Activation of muscarinic receptors by carbachol(CCh) stimulated mouse duodenal Isc, which was significantly inhibited in Ca2+-free serosal solution and by several selective store-operated Ca2+ channels(SOC) blockers added to the serosal side of duodenal tissues...
January 9, 2018: Oncotarget
Bernard T Drumm, Benjamin E Rembetski, Caroline A Cobine, Salah A Baker, Gerard P Sergeant, Mark A Hollywood, Keith D Thornbury, Kenton M Sanders
Urethral smooth muscle cells (USMC) generate myogenic tone and contribute to urinary continence. Currently, little is known about Ca2+ signalling in USMC in situ, and therefore little is known about the source(s) of Ca2+ required for excitation-contraction coupling. We characterized Ca2+ signalling in USMC within intact urethral muscles using a genetically encoded Ca2+ sensor, GCaMP3, expressed selectively in USMC. USMC fired spontaneous intracellular Ca2+ waves that did not propagate cell-to-cell across muscle bundles...
January 31, 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
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
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
S Shaikh, R Troncoso, D Mondaca-Ruff, V Parra, L Garcia, M Chiong, S Lavandero
Stromal-interaction molecule 1 (STIM1)-mediated store-operated Ca2+ entry (SOCE) plays a key role in mediating cardiomyocyte hypertrophy, both in vitro and in vivo. Moreover, there is growing support for the contribution of SOCE to the Ca2+ overload associated with ischemia/reperfusion injury. Therefore, STIM1 inhibition is proposed as a novel target for controlling both hypertrophy and ischemia/reperfusion-induced Ca2+ overload. Our aim was to evaluate the effect of ML9, a STIM1 inhibitor, on cardiomyocyte viability...
January 11, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
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
Jin-Nan Zhong, Lan Lan, Yi-Fei Chen, Ge Huang, Guang-Zhen He, Jiong Yang, Ya-Dong Gao
BACKGROUND: Circulating fibrocytes (CFs) have been shown to participate in subepithelial fibrosis of asthma with chronic airflow limitation by acting as an important source of fibroblasts deposited beneath airway epithelia. Serum amyloid P (SAP) is an innate inhibitor of fibrocytes differentiation. Store-operated Ca2+ entry (SOCE) is the major Ca2+ influx of non-excitable cells. In this study, the role of SOCE in the regulation of fibrocytes differentiation and the effects of Th2 cytokine IL-4 and SAP on SOCE of fibrocytes were investigated...
July 12, 2017: Pharmacological Reports: PR
Jose J Lopez, Letizia Albarrán, Isaac Jardín, Jose Sanchez-Collado, Pedro C Redondo, Nuria Bermejo, Regis Bobe, Tarik Smani, Juan A Rosado
OBJECTIVE: Here, we provide evidence for the role of FLNA (filamin A) in the modulation of store-operated calcium entry (SOCE). APPROACH AND RESULTS: SOCE is a major mechanism for calcium influx controlled by the intracellular Ca2+ stores. On store depletion, the endoplasmic reticulum calcium sensor STIM1 (stromal interaction molecule 1) redistributes into puncta at endoplasmic reticulum/plasma membrane junctions, a process supported by the cytoskeleton, where it interacts with the calcium channels; however, the mechanism for fine-tuning SOCE is not completely understood...
December 28, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
Shlesha Richhariya, Gaiti Hasan
Ral is a small GTPase of the Ras superfamily that is important for a number of cellular functions. Recently, we found that expression of Ral is regulated by store-operated calcium entry (SOCE) in Drosophila neurons. In this study, through genetic and behavioural experiments, we show that Ral function is required in differentiated muscles for flight. Reducing Ral function in muscles, specifically reduced duration of flight bouts but not other motor functions, like climbing. Interestingly, unlike in the nervous system, Ral expression in the muscle is not regulated by SOCE...
December 28, 2017: Small GTPases
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