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https://www.readbyqxmd.com/read/28803243/lithium-sensitivity-of-store-operated-ca2-entry-and-survival-of-fibroblasts-isolated-from-chorea-acanthocytosis-patients
#1
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
https://www.readbyqxmd.com/read/28775294/anti-allergic-activity-of-glycyrrhizic-acid-on-ige-mediated-allergic-reaction-by-regulation-of-allergy-related-immune-cells
#2
Shiwen Han, Lu Sun, Feng He, Huilian Che
Glycyrrhizic acid (GA), the major bioactive triterpene glycoside of glycyrrhiza, has been shown to possess a wide range of pharmacological properties, including anti-inflammatory and anti-viral properties. However, few studies have examined the anti-allergic activity and exact mechanism of action of GA. In the present work, the anti-allergic activity and possible mechanisms of action of GA on an immunoglobulin (Ig) E-mediated allergic reaction has been studied using three models of allergic reaction in vivo and in vitro...
August 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28761977/calcineurin-inhibitors-regulate-fibroblast-growth-factor-23-fgf23-synthesis
#3
Ludmilla Bär, Claudia Großmann, Michael Gekle, Michael Föller
Fibroblast growth factor 23 (FGF23) inhibits renal phosphate reabsorption and calcitriol formation, effects depending on Klotho as a co-receptor for FGF23. In addition, FGF23/Klotho strongly influences aging and the onset of age-associated diseases. The synthesis of FGF23 by bone cells is induced by store-operated Ca(2+) entry (SOCE) through Orai1 in UMR106 osteoblast-like cells. Ca(2+) entry activates the phosphatase calcineurin in many cell types which dephosphorylates nuclear factor of activated T cells (NFAT) thereby stimulating its transcriptional activity...
July 31, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28743945/lithium-sensitive-orai1-expression-store-operated-ca-2-entry-and-suicidal-death-of-neurons-in-chorea-acanthocytosis
#4
Lisann Pelzl, Stefan Hauser, Bhaeldin Elsir, Basma Sukkar, Itishri Sahu, Yogesh Singh, Philip Höflinger, Rosi Bissinger, Mohamed Jemaà, Christos Stournaras, Ludger Schöls, Florian Lang
Chorea-Acanthocytosis (ChAc), a neurodegenerative disorder, results from loss-of-function-mutations of chorein-encoding gene VPS13A. In tumour cells chorein up-regulates ORAI1, a Ca(2+)-channel accomplishing store operated Ca(2+)-entry (SOCE) upon stimulation by STIM1. Furthermore SOCE could be up-regulated by lithium. The present study explored whether SOCE impacts on neuron apoptosis. Cortical neurons were differentiated from induced pluripotent stem cells generated from fibroblasts of ChAc patients and healthy volunteers...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28732182/stim1-regulates-enamel-mineralization-and-ameloblast-modulation
#5
Y Furukawa, N Haruyama, M Nikaido, M Nakanishi, N Ryu, M Oh-Hora, K Kuremoto, K Yoshizaki, Y Takano, I Takahashi
Loss-of-function mutations in the Ca(2+) release-activated Ca(2+) channel genes ORAI1 and STIM1 abolish store-operated Ca(2+) entry (SOCE) and result in ectodermal dysplasia with amelogenesis imperfecta. However, because of the limited availability of patient tissue, analyses of enamel mineralization or possible changes in ameloblast function or morphology have not been possible. Here, we generated mice with ectodermal tissue-specific deletion of Stim1 ( Stim1 cKO [conditional knockout]), Stim2 ( Stim2 cKO), and Stim1 and Stim2 ( Stim1/2 cKO) and analyzed their enamel phenotypes as compared with those of control ( Stim1/2(fl/fl)) animals...
July 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28728119/nf-%C3%AE%C2%BAb-mediated-inflammation-correlates-with-calcium-overload-under-arsenic-trioxide-induced-myocardial-damage-in-gallus-gallus
#6
Siwen Li, Yu Wang, Hongjing Zhao, Ying He, Jinglun Li, Guangshun Jiang, Mingwei Xing
Arsenic is a known environmental pollutant and highly hazardous toxin to human health. Due to the biological accumulation, arsenic produces a variety of cardiovascular diseases. However, the exact mechanism is still unclear. Here, our objective was to evaluate myocardial damage and determine the potential mechanism under arsenic exposure in chickens. Arsenic trioxide (As2O3) (1.25 mg/kg BW, corresponding 15 mg/kg feed) was administered as basal diet to male Hy-line chickens (one-day-old) for 4, 8 and 12 weeks...
October 2017: Chemosphere
https://www.readbyqxmd.com/read/28726786/calcium-binding-protein-s100a14-induces-differentiation-and-suppresses-metastasis-in-gastric-cancer
#7
Min Zhu, Hongyi Wang, Jiantao Cui, Wenmei Li, Guo An, Yuanming Pan, Qingying Zhang, Rui Xing, Youyong Lu
S100A14 is a calcium-binding protein involved in cell proliferation and differentiation as well as the metastasis of human tumors. In this study, we characterized the regulation of S100A14 expression between biological signatures and clinical pathological features in gastric cancer (GC). Our data demonstrated that S100A14 induced the differentiation of GC by upregulating the expression of E-cadherin and PGII. Moreover, S100A14 expression negatively correlated with cell migration and invasion in in vitro and in vivo experimental models...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28724757/molecular-anatomy-of-the-early-events-in-stim1-activation-oligomerization-or-conformational-change
#8
Marek K Korzeniowski, Eva Wisniewski, Barbara Baird, David Holowka, Tamas Balla
Decreased luminal ER Ca(2+) concentration triggers oligomerization and clustering of the ER Ca(2+)-sensor, STIM1 to promote its association with plasma membrane Orai1 Ca(2+) channels leading to increased Ca(2+) influx. A key step in STIM1 activation is the release of its SOAR domain from an intramolecular clamp formed with the STIM1 first coiled-coil (CC1) region. Using a truncated STIM1(1-343) molecule that captures or releases the isolated SOAR domain depending on luminal ER Ca(2+) concentrations, we analyzed the early molecular events that control the intramolecular clamp formed between the CC1 and SOAR domains...
July 19, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28723646/collagen-type-1-promotes-survival-of-human-breast-cancer-cells-by-overexpressing-kv10-1-potassium-and-orai1-calcium-channels-through-ddr1-dependent-pathway
#9
Mehdi Badaoui, Cloé Mimsy-Julienne, Charles Saby, Laurence Van Gulick, Marta Peretti, Pierre Jeannesson, Hamid Morjani, Halima Ouadid-Ahidouch
Collagen type 1 is among the tumor microenvironment (TM) factors, that regulates proliferation, survival, migration and invasion. Ion channels are key players in interactions between tumor cells and TM. Kv10.1 has been shown to play an essential role in breast cancer cell proliferation and migration by permitting Ca2+ influx notably via Orai1. Here, we show that human breast cancer (BC) cells growing, in culture media completely devoid of the serum and seeded on collagen 1 coating, exhibited less apoptotic rate and a decrease in Bax expression when compared to those grown on plastic...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28704809/istaroxime-inhibits-motility-and-down-regulates-orai1-expression-soce-and-fak-phosphorylation-in-prostate-cancer-cells
#10
Matias Julian Stagno, Nefeli Zacharopoulou, Jonas Bochem, Anna Tsapara, Lisann Pelzl, Tamer Al-Maghout, Galatea Kallergi, Saad Alkahtani, Konstantinos Alevizopoulos, Konstantinos Dimas, Theodora Calogeropoulou, Steven W Warmann, Florian Lang, Evi Schmid, Christos Stournaras
BACKGROUND/AIMS: Istaroxime is a validated inotropic Na+/K+ ATPase inhibitor currently in development for the treatment of various cardiac conditions. Recent findings established that this steroidal drug exhibits potent apoptotic responses in prostate tumors in vitro and in vivo, by affecting key signaling orchestrating proliferation and apoptosis, such as c-Myc and caspase 3, Rho GTPases and actin cytoskeleton dynamics. In the present study we examined whether istaroxime is affecting cell motility and analyzed the underlying mechanism in prostate tumor cells...
July 14, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28698564/homer-binds-to-orai1-and-trpc-channels-in-the-neointima-and-regulates-vascular-smooth-muscle-cell-migration-and-proliferation
#11
Shuping Jia, Miguel Rodriguez, Arthur G Williams, Joseph P Yuan
The molecular components of store-operated Ca(2+) influx channels (SOCs) in proliferative and migratory vascular smooth muscle cells (VSMCs) are quite intricate with many channels contributing to SOCs. They include the Ca(2+)-selective Orai1 and members of the transient receptor potential canonical (TRPC) channels, which are activated by the endoplasmic reticulum Ca(2+) sensor STIM1. The scaffolding protein Homer assembles SOC complexes, but its role in VSMCs is not well understood. Here, we asked whether these SOC components and Homer1 are present in the same complex in VSMCs and how Homer1 contributes to VSMC SOCs, proliferation, and migration leading to neointima formation...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28694529/the-production-of-fibroblast-growth-factor-23-is-controlled-by-tgf-%C3%AE-2
#12
Martina Feger, Philipp Hase, Bingbing Zhang, Frank Hirche, Philipp Glosse, Florian Lang, Michael Föller
Transforming growth factor-β (TGF-β) is a cytokine produced by many cell types and implicated in cell growth, differentiation, apoptosis, and inflammation. It stimulates store-operated calcium entry (SOCE) through the calcium release-activated calcium (CRAC) channel Orai1/Stim1 in endometrial Ishikawa cells. Bone cells generate fibroblast growth factor (FGF) 23, which inhibits renal phosphate reabsorption and 1,25(OH)2D3 formation in concert with its co-receptor Klotho. Moreover, Klotho and FGF23 counteract aging and age-related clinical conditions...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28637791/store-operated-calcium-entry-suppressed-tgf%C3%AE-1-smad3-signaling-pathway-in-glomerular-mesangial-cells
#13
Sarika Chaudhari, Weizu Li, Yanxia Wang, Hui Jiang, Yuhong Ma, Mark E Davis, Jonathan E Zuckerman, Rong Ma
Our previous study demonstrated that the abundance of extracellular matrix proteins was suppressed by store-operated Ca2+ entry in mesangial cells (MCs). The present study was conducted to investigate the underlying mechanism focused on the transforming growth factor beta 1 (TGFβ1) - Smad3 pathway, a critical pathway for ECM expansion in diabetic kidneys. We hypothesized that SOCE suppressed ECM protein expression by inhibiting this pathway in MCs. In cultured human MCs, we observed that TGFβ1 (5 ng/ml for 15 hours) significantly increased Smad3 phosphorylation as evaluated by immunoblot...
June 21, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28636748/e-cadherin-mediates-uvr-and-calcium-induced-melanin-transfer-in-human-skin-cells
#14
Suman K Singh, Richard Baker, Stephen K Sikkink, Carine Nizard, Sylvianne Schnebert, Robin Kurfurst, Desmond J Tobin
Skin pigmentation is directed by epidermal-melanin units, characterized by long-lived and dendritic epidermal melanocytes (MC) that interact with viable keratinocytes (KC) to contribute melanin to the epidermis. Previously we reported that MC:KC contact is required for melanosome transfer, that this can be enhanced by filopodial and by UVR/UVA irradiation, which can up-regulate melanosome transfer via Myosin X-mediated control of MC filopodia. Both MC and KC express Ca(2+) -dependent E-cadherins. These homophilic adhesion contacts induce transient increases in intra-KC Ca(2+) , while ultraviolet radiation (UVR) raises intra-MC Ca(2+) via calcium selective ORAI1 ion channels; both are associated with regulating melanogenesis...
June 21, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28634110/pharmacological-rescue-of-ductal-cftr-rescue-pancreatic-and-salivary-glands-acinar-cells-and-tissue-function-in-mouse-models-of-autoimmune-diseases
#15
Mei Zeng, Mitchell Szymczak, Malini Ahuja, Changyu Zheng, Hongen Yin, William Swaim, John A Chiorini, Robert J Bridges, Shmuel Muallem
BACKGROUND & AIMS: Sjögren's syndrome and autoimmune pancreatitis (AIP) are disorders with decreased function of salivary, lacrimal glands, and the exocrine pancreas. NOD/ShiLTJ mice and mice transduced with the cytokine BMP6 develop Sjögren's syndrome and chronic pancreatitis and MRL/Mp mice are models of AIP. CFTR is a ductal Cl(-) channel essential for ductal fluid and HCO3(-) secretion. We used these models to ask: is CFTR expression altered in these diseases, does correction of CFTR correct gland function, and most notably, does correcting ductal function correct acinar function...
June 17, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28633876/hemophagocytic-lymphohistiocytosis-as-presenting-manifestation-of-profound-combined-immunodeficiency-due-to-an-orai1-mutation
#16
Christian Klemann, Sandra Ammann, Miriam Heizmann, Sebastian Fuchs, Sebastian F Bode, Maximilian Heeg, Hans Fuchs, Kai Lehmberg, Udo Zur Stadt, Claudia Roll, Thomas Vraetz, Carsten Speckmann, Myriam Ricarda Lorenz, Klaus Schwarz, Jan Rohr, Stefan Feske, Stephan Ehl
No abstract text is available yet for this article.
June 19, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28629579/role-of-soce-architects-stim-and-orai-proteins-in-cell-death
#17
REVIEW
Jyoti Tanwar, Rajender K Motiani
Calcium (Ca(2+)) signaling plays a critical role in regulating plethora of cellular functions including cell survival, proliferation and migration. The perturbations in cellular Ca(2+) homeostasis can lead to cell death either by activating autophagic pathways or through induction of apoptosis. Endoplasmic reticulum (ER) is the major storehouse of Ca(2+) within cells and a number of physiological agonists mediate ER Ca(2+) release by activating IP3 receptors (IP3R). This decrease in ER Ca(2+) levels is sensed by STIM, which physically interacts and activates plasma membrane Ca(2+) selective Orai channels...
June 9, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28564609/sequential-steps-of-crac-channel-activation
#18
Raz Palty, Zhu Fu, Ehud Y Isacoff
Interaction between the endoplasmic reticulum protein STIM1 and the plasma membrane channel ORAI1 generates calcium signals that are central for diverse cellular functions. How STIM1 binds and activates ORAI1 remains poorly understood. Using electrophysiological, optical, and biochemical techniques, we examined the effects of mutations in the STIM1-ORAI1 activating region (SOAR) of STIM1. We find that SOAR mutants that are deficient in binding to resting ORAI1 channels are able to bind to and boost activation of partially activated ORAI1 channels...
May 30, 2017: Cell Reports
https://www.readbyqxmd.com/read/28545724/the-role-of-ca-2-in-cell-death-caused-by-oxidative-glutamate-toxicity-and-ferroptosis
#19
REVIEW
Pamela Maher, Klaus van Leyen, Partha Narayan Dey, Birgit Honrath, Amalia Dolga, Axel Methner
Ca(2+) ions play a fundamental role in cell death mediated by oxidative glutamate toxicity or oxytosis, a form of programmed cell death similar and possibly identical to other forms of cell death like ferroptosis. Ca(2+) influx from the extracellular space occurs late in a cascade characterized by depletion of the intracellular antioxidant glutathione, increases in cytosolic reactive oxygen species and mitochondrial dysfunction. Here, we aim to compare oxidative glutamate toxicity with ferroptosis, address the signaling pathways that culminate in Ca(2+) influx and cell death and discuss the proteins that mediate this...
May 12, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28544117/increased-expression-of-stim1-orai1-in-platelets-of-stroke-patients-predictive-of-poor-outcomes
#20
M Dong, N Zheng, L J Ren, H Zhou, J Liu
BACKGROUND AND PURPOSE: The platelet activation that is mediated by store-operated Ca(2+) entry via stromal interaction molecule (STIM1) and Orai1 Ca(2+) influx channels has been shown to play a key role in ischaemic stroke (IS). This study aimed to evaluate the impact of platelet STIM1/Orai1 protein expression on outcomes of IS. METHODS: A total of 160 patients with acute non-cardioembolic IS, among whom 45 patients had small-vessel diseases and 115 patients had large-vessel diseases, were evaluated...
May 23, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
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