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https://www.readbyqxmd.com/read/28497275/na-ca-2-exchangers-and-orai-channels-jointly-refill-endoplasmic-reticulum-er-ca-2-via-er-nanojunctions-in-vascular-endothelial-cells
#1
Cristiana M L Di Giuro, Niroj Shrestha, Roland Malli, Klaus Groschner, Cornelis van Breemen, Nicola Fameli
We investigated the role of Na(+)/ Ca(2+) exchange (NCX) in the refilling of endoplasmic reticulum (ER) Ca(2+) in vascular endothelial cells under various conditions of cell stimulation and plasma membrane (PM) polarization. Better understanding of the mechanisms behind basic ER Ca(2+) content regulation is important, since current hypotheses on the possible ultimate causes of ER stress point to deterioration of the Ca(2+) transport mechanism to/from ER itself. We measured [Ca(2+)]i temporal changes by Fura-2 fluorescence under experimental protocols that inhibit a host of transporters (NCX, Orai, non-selective transient receptor potential canonical (TRPC) channels, sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA), Na(+)/ K(+) ATPase (NKA)) involved in the Ca(2+) communication between the extracellular space and the ER...
May 11, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28492364/na-influx-via-orai1-inhibits-intracellular-atp-induced-mtorc2-signaling-to-disrupt-cd4-t-cell-gene-expression-and-differentiation
#2
Yong Miao, Jaya Bhushan, Adish Dani, Monika Vig
T cell effector functions require sustained calcium influx. However, the signaling and phenotypic consequences of non-specific sodium permeation via calcium channels remain unknown. α-SNAP is a crucial component of Orai1 channels, and its depletion disrupts the functional assembly of Orai1 multimers. Here we show that α-SNAP hypomorph, hydrocephalos with hopping gait, Napa(hyh/hyh) mice harbor significant defects in CD4 T cell gene expression and Foxp3 regulatory T cell (Treg) differentiation. Mechanistically, TCR stimulation induced rapid sodium influx in Napa(hyh/hyh) CD4 T cells, which reduced intracellular ATP, [ATP]i...
May 11, 2017: ELife
https://www.readbyqxmd.com/read/28487655/gastrodin-inhibits-store-operated-ca-2-entry-and-alleviates-cardiac-hypertrophy
#3
Changbo Zheng, Chun-Yin Lo, Zhaoyue Meng, Zhichao Li, Mingkui Zhong, Peng Zhang, Jun Lu, Zhaoxiang Yang, Fuman Yan, Yunting Zhang, Yu Huang, Xiaoqiang Yao
Cardiac hypertrophy is a major risk factor for heart failure, which are among the leading causes of human death. Gastrodin is a small molecule that has been used clinically to treat neurological and vascular diseases for many years without safety issues. In the present study, we examined protective effect of gastrodin against cardiac hypertrophy and explored the underlying mechanism. Phenylephrine and angiotensin II were used to induce cardiac hypertrophy in a mouse model and a cultured cardiomyocyte model...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28486663/ca2-signaling-machinery-is-present-at-intercellular-junctions-and-structures-associated-with-junction-turnover-in-rat-sertoli-cells
#4
Kevin Lyon, Arlo Adams, Matthew Piva, Parisa Asghari, Edwin D Moore, A Wayne Vogl
The endoplasmic reticulum (ER) is a prominent organelle in Sertoli cells. It is an integral component of unique adhesion junctions (ectoplasmic specializations-ESs) in this cell type, and is closely associated with structures termed tubulobulbar complexes (TBCs) that internalize intercellular junctions during sperm release and during the translocation of spermatocytes through the blood-testis barrier. A role for the ER in Ca2+ regulation at ESs and TBCs has been suspected, but evidence for this function has proved elusive...
May 8, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28450355/orai1-controls-the-unique-adjustment-of-lymphatics-to-fluid-flow
#5
EDITORIAL
Sinem Karaman, Kari Alitalo
No abstract text is available yet for this article.
April 28, 2017: Circulation Research
https://www.readbyqxmd.com/read/28446591/nfat5-sensitive-orai1-expression-and-store-operated-ca-2-entry-in-megakaryocytes
#6
Itishri Sahu, Lisann Pelzl, Basma Sukkar, Hajar Fakhri, Tamer Al-Maghout, Hang Cao, Stefan Hauser, Ravi Gutti, Meinrad Gawaz, Florian Lang
The transcription factor NFAT5 is up-regulated in several clinical disorders including dehydration. NFAT5-sensitive genes include serum and glucocorticoid-inducible kinase (SGK)-1. The kinase is a powerful regulator of Orai1, a Ca(2+)-channel accomplishing store-operated Ca(2+)-entry (SOCE). Orai1 is stimulated after intracellular store depletion by the Ca(2+) sensors stromal interaction molecule (STIM)-1, or STIM2, or both. In the present study, we explored whether nuclear factor of activated T cell (NFAT)-5 influences Ca(2+)-signaling in megakaryocytes...
April 26, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28416610/evidence-for-shear-mediated-ca-2-entry-through-mechanosensitive-cation-channels-in-human-platelets-and-a-megakaryocytic-cell-line
#7
Zeki Ilkan, Joy R Wright, Alison H Goodall, Jonathan M Gibbins, Chris I Jones, Martyn P Mahaut-Smith
The role of mechanosensitive (MS) Ca(2+)-permeable ion channels in platelets is unclear, despite the importance of shear stress in platelet function and life-threatening thrombus formation. We therefore sought to investigate the expression and functional relevance of MS channels in human platelets. The effect of shear stress on Ca(2+) entry in human platelets and Meg-01 megakaryocytic cells loaded with Fluo-3 was examined by confocal microscopy. Cells were attached to microscope slides within flow chambers that allowed applications of physiological and pathological shear stress...
April 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28403042/altered-mitochondrial-function-capacitative-calcium-entry-and-contractions-in-the-aorta-of-hypertensive-rats
#8
Iago Méndez-López, Guilherme H S Bomfim, Diego C Musial, Juan A Arranz-Tagarro, Juan P Velasco-Martín, Javier Regadera, Neide H Jurkiewicz, Aron Jurkiewicz, Antonio G García, Fernando J Padín
OBJECTIVE: It has been suggested that Ca entry through store-operated Ca channels (SOCs) is regulated by a dynamic interplay between the endoplasmic reticulum Ca stores and the mitochondria. These relationships drive the activation and inactivation of SOCs, yet it remains unclear whether this regulation of SOCs by mitochondria is altered in the aorta of spontaneously hypertensive rats (SHRs). METHODS: We performed a thorough study of the mitochondrial membrane potential, the ability of mitochondria to deal with cytosolic Ca, capacitative Ca entry (CCE), and stromal interaction molecule 1 (STIM1) and calcium release-activated calcium modulator 1 (orai1) protein expression, as well as the contractile capacity of aortic rings, in normotensive Wistar Kyoto rats (WKYs) and SHRs...
April 11, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28352332/inhibitory-effect-of-salvia-plebeia-leaf-extract-on-ultraviolet-induced-photoaging-associated-ion-channels-and-enzymes
#9
You-Jin Chang, Dong-Ung Lee, Da Yeong Nam, Sung Min Cho, Seungug Hong, Joo Hyun Nam, Woo Kyung Kim
In traditional Korean/Asian medicine, Salvia plebeia R.Br. (S. plebeia) leaves are used to treat inflammatory diseases, including dermatitis, cough, asthma and toothache. Recently, S. plebeia leaves have been applied in skin care, as they promote skin lightening and elasticity. Therefore, the present study investigated the anti-aging effects of S. plebeia leaf methanolic extract and its fractions (dichloromethane, ethylacetate and n-butanol). The results of a whole-cell patch clamp analysis indicated that the methanolic extract mediated ultraviolet (UV)-induced photoaging-associated ion channels, transient receptor potential vanilloid 1 (TRPV1) and calcium release-activated calcium channel protein 1 (ORAI1) channel activity in HEK293T cells overexpressing TRPV1 or ORAI1 and STIM1...
February 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28351952/shaping-the-gut-microbiome-from-the-pancreas
#10
Wei Wong
The intracellular Ca(2+) channel Orai1 in pancreatic acinar cells helps to suppress inflammation-associated bacterial strains in the gut.
March 28, 2017: Science Signaling
https://www.readbyqxmd.com/read/28341841/regulation-of-membrane-ruffling-by-polarized-stim1-and-orai1-in-cortactin-rich-domains
#11
Aida M Lopez-Guerrero, Patricia Tomas-Martin, Carlos Pascual-Caro, Thomas Macartney, Alejandro Rojas-Fernandez, Graeme Ball, Dario R Alessi, Eulalia Pozo-Guisado, Francisco Javier Martin-Romero
Cell motility and migration requires the reorganization of the cortical cytoskeleton at the leading edge of cells and extracellular Ca(2+) entry is essential for this reorganization. However the molecular nature of the regulators of this pathway is unknown. This work contributes to understanding the role of STIM1 and ORAI1 in the promotion of membrane ruffling by showing that phospho-STIM1 localizes at the leading edge of cells, and that both phospho-STIM1 and ORAI1 co-localize with cortactin (CTTN), a regulator of the cytoskeleton at membrane ruffling areas...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28331181/multi-walled-carbon-nanotubes-act-as-a-chemokine-and-recruit-macrophages-by-activating-the-plc-ip3-crac-channel-signaling-pathway
#12
Hui Li, Xiao-Qiu Tan, Li Yan, Bo Zeng, Jie Meng, Hai-Yan Xu, Ji-Min Cao
The impact of nanomaterials on immune cells is gaining attention but is not well documented. Here, we report a novel stimulating effect of carboxylated multi-walled carbon nanotubes (c-MWCNTs) on the migration of macrophages and uncover the underlying mechanisms, especially the upstream signaling, using a series of techniques including transwell migration assay, patch clamp, ELISA and confocal microscopy. c-MWCNTs dramatically stimulated the migration of RAW264.7 macrophages when endocytosed, and this effect was abolished by inhibiting phospholipase C (PLC) with U-73122, antagonizing the IP3 receptor with 2-APB, and blocking calcium release-activated calcium (CRAC) channels with SK&F96365...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28325835/picomolar-selective-and-subtype-specific-small-molecule-inhibition-of-trpc1-4-5-channels
#13
Hussein N Rubaiy, Melanie J Ludlow, Matthias Henrot, Hannah J Gaunt, Katarina Miteva, Sin Yin Cheung, Yasuyuki Tanahashi, Nurasyikin Hamzah, Katie E Musialowski, Nicola M Blythe, Hollie L Appleby, Marc A Bailey, Lynn McKeown, Roger Taylor, Richard Foster, Herbert Waldmann, Peter Nussbaumer, Mathias Christmann, Robin S Bon, Katsuhiko Muraki, David J Beech
The concentration of free cytosolic Ca(2+) and the voltage across the plasma membrane are major determinants of cell function. Ca(2+)-permeable non-selective cationic channels are known to regulate these parameters but understanding of these channels remains inadequate. Here we focus on Transient Receptor Potential Canonical 4 and 5 proteins (TRPC4 and TRPC5) which assemble as homomers or heteromerize with TRPC1 to form Ca(2+)-permeable non-selective cationic channels in many mammalian cell types. Multiple roles have been suggested including in epilepsy, innate fear, pain and cardiac remodeling but limitations in tools to probe these channels have restricted progress...
March 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28301277/evidence-that-orai1-does-not-contribute-to-store-operated-trpc1-channels-in-vascular-smooth-muscle-cells
#14
Jian Shi, Francesc Miralles, Jean-Pierre Kinet, Lutz Birnbaumer, William A Large, Anthony P Albert
Ca(2+)-permeable store-operated channels (SOCs) mediate Ca(2+) entry pathways which are involved in many cellular functions such as contraction, growth, and proliferation. Prototypical SOCs are formed of Orai1 proteins and are activated by the endo/sarcoplasmic reticulum Ca(2+) sensor stromal interaction molecule 1 (STIM1). There is considerable debate about whether canonical transient receptor potential 1 (TRPC1) proteins also form store-operated channels (SOCs), and if they do, is Orai1 involved. We recently showed that stimulation of TRPC1-based SOCs involves store depletion inducing STIM1-evoked Gαq/PLCβ1 activity in contractile vascular smooth muscle cells (VSMCs)...
March 16, 2017: Channels
https://www.readbyqxmd.com/read/28298362/negative-regulation-of-smad1-pathway-and-collagen-iv-expression-by-store-operated-ca2-entry-in-glomerular-mesangial-cells
#15
Peiwen Wu, Yuezhong Ren, Yuhong Ma, Yanxia Wang, Hui Jiang, Sarika Chaudhari, Mark E Davis, Jonathan E Zuckerman, Rong Ma
Collagen IV (Col IV) is a major component of expanded glomerular extracellular matrix in diabetic nephropathy and Smad1 is a key molecule regulating Col IV expression in mesangial cells (MCs). The present study was conducted to determine if Smad1 pathway and Col IV protein abundance were regulated by store-operated Ca2+ entry (SOCE). In cultured human MCs, pharmacological inhibition of SOCE significantly increased the total amount of Smad1 protein. Activation of SOCE blunted high glucose-increased Smad1 protein content...
March 15, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28296184/long-term-administration-of-pyridostigmine-attenuates-pressure-overload-induced-cardiac-hypertrophy-by-inhibiting-calcineurin-signalling
#16
Yi Lu, Ming Zhao, Jin-Jun Liu, Xi He, Xiao-Jiang Yu, Long-Zhu Liu, Lei Sun, Li-Na Chen, Wei-Jin Zang
Cardiac hypertrophy is associated with autonomic imbalance, characterized by enhanced sympathetic activity and withdrawal of parasympathetic control. Increased parasympathetic function improves ventricular performance. However, whether pyridostigmine, a reversible acetylcholinesterase inhibitor, can offset cardiac hypertrophy induced by pressure overload remains unclear. Hence, this study aimed to determine whether pyridostigmine can ameliorate pressure overload-induced cardiac hypertrophy and identify the underlying mechanisms...
March 10, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28294127/orai2-modulates-store-operated-calcium-entry-and-t-cell-mediated-immunity
#17
Martin Vaeth, Jun Yang, Megumi Yamashita, Isabelle Zee, Miriam Eckstein, Camille Knosp, Ulrike Kaufmann, Peter Karoly Jani, Rodrigo S Lacruz, Veit Flockerzi, Imre Kacskovics, Murali Prakriya, Stefan Feske
Store-operated Ca(2+) entry (SOCE) through Ca(2+) release-activated Ca(2+) (CRAC) channels is critical for lymphocyte function and immune responses. CRAC channels are hexamers of ORAI proteins that form the channel pore, but the contributions of individual ORAI homologues to CRAC channel function are not well understood. Here we show that deletion of Orai1 reduces, whereas deletion of Orai2 increases, SOCE in mouse T cells. These distinct effects are due to the ability of ORAI2 to form heteromeric channels with ORAI1 and to attenuate CRAC channel function...
March 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28293066/udp-induced-phagocytosis-and-atp-stimulated-chemotactic-migration-are-impaired-in-stim1-microglia-in-vitro-and-in-vivo
#18
Hye Min Lim, Heo Woon, Jung Woo Han, Yoshihiro Baba, Tomohiro Kurosaki, Min Goo Lee, Joo Young Kim
STIM1 is the only currently known intracellular calcium sensor that functions as the calcium influx regulator controlling immune cell activation. STIM1 function in immune cell calcium signalling has been studied extensively; however, its role in microglia, innate immune cells in brain, has not been fully understood. Here, we report that STIM1(-/-) murine microglia lost store-operated calcium influx and displayed aberrant immunological functions. Microglial functions regulated by chronic and global [Ca(2+)]i changes were reduced significantly, including cytokine releases and opsonin-dependent phagocytosis...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28290212/spirodela-polyrhiza-extract-modulates-the-activation-of-atopic-dermatitis-related-ion-channels-orai1-and-trpv3-and-inhibits-mast-cell-degranulation
#19
Joo Hyun Nam, Hyo Won Jung, Young-Won Chin, Won-Mo Yang, Hyo Sang Bae, Woo Kyung Kim
CONTEXT: Spirodela polyrhiza (L.) Schleid. (Lemnaceae), Spirodelae Herba (SH), has been known to relieve inflammation, urticaria and skin symptoms including pruritus, eczema and rash. OBJECTIVE: The effects of SH extract on two calcium ion channels, Orai1 and TRPV3, and their potential as novel therapeutics for atopic dermatitis (AD) were investigated. The regulatory role of Orai1 on mast cell degranulation was evaluated. MATERIALS AND METHODS: The dried leaves of SH were extracted by 70% methanol...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28286123/the-enhancement-of-txa2-receptors-mediated-contractile-response-in-intrarenal-artery-dysfunction-in-type-2-diabetic-mice
#20
Su-Juan Kuang, Jie-Sheng Qian, Hui Yang, Fang Rao, Xiao-Yan Chen, Meng-Zhen Zhang, Zhi-Xin Shan, Qiu-Xiong Lin, Yu-Mei Xue, Shu-Lin Wu, Li Jiang, Chun-Bo Chen, Chun-Yu Deng
Thromboxane A2 (TXA2) has been implicated in the pathogenesis of diabetic vascular complications, although the underlying mechanism remains unclear. The present study investigated the alterations in TXA2 receptor signal transduction in type 2 diabetic renal arteries. The contraction of renal arterial rings in control (db/m+) mice and type 2 diabetic (db/db) mice was measured by a Multi Myograph System. Intracellular calcium concentration ([Ca(2+)]i) in vascular smooth muscle cells was measured by Fluo-4/AM dye and confocal laser scanning microscopy...
March 9, 2017: European Journal of Pharmacology
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