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https://www.readbyqxmd.com/read/29778900/hereditary-sensory-neuropathy-type-1-associated-deoxysphingolipids-cause-neurotoxicity-acute-calcium-handling-abnormalities-and-mitochondrial-dysfunction-in-vitro
#1
Emma R Wilson, Umaiyal Kugathasan, Andrey Y Abramov, Alex J Clark, David L H Bennett, Mary M Reilly, Linda Greensmith, Bernadett Kalmar
Hereditary sensory neuropathy type 1 (HSN-1) is a peripheral neuropathy most frequently caused by mutations in the SPTLC1 or SPTLC2 genes, which code for two subunits of the enzyme serine palmitoyltransferase (SPT). SPT catalyzes the first step of de novo sphingolipid synthesis. Mutations in SPT result in a change in enzyme substrate specificity, which causes the production of atypical deoxysphinganine and deoxymethylsphinganine, rather than the normal enzyme product, sphinganine. Levels of these abnormal compounds are elevated in blood of HSN-1 patients and this is thought to cause the peripheral motor and sensory nerve damage that is characteristic of the disease, by a largely unresolved mechanism...
May 17, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29777594/il-3-producing-basophils-are-required-to-exacerbate-airway-hyper-responsiveness-in-a-murine-inflammatory-model
#2
Rachel Rignault-Bricard, François Machavoine, Salah Mecheri, Olivier Hermine, Elke Schneider, Michel Dy, Maria Leite-de-Moraes
BACKGROUND: Basophils are commonly associated with allergic responses because of their ability to produce large amounts of pro-Th2 cytokines and histamine. However, the mechanisms through which bone marrow-resident basophils (BMRB) become fully competent cytokine and histamine producers in response to IgE crosslinking are poorly understood. Here, we sought to determine the role of IL-3 in promoting pro-Th2 basophils. METHODS: BMRB and basophils exposed to IL-3 in vitro and in vivo were evaluated for their production of Th2 cytokines and histamine in response to FcεRI crosslinking on both protein and gene expression levels...
May 19, 2018: Allergy
https://www.readbyqxmd.com/read/29774408/possible-association-of-cag-repeat-polymorphism-in-kcnn3-encoding-the-potassium-channel-sk3-with-oxaliplatin-induced-neurotoxicity
#3
Benjamin Anon, Bérenger Largeau, Alban Girault, Aurélie Chantome, Morgane Caulet, Clémence Perray, Driffa Moussata, Christophe Vandier, Chantal Barin-Le Guellec, Thierry Lecomte
INTRODUCTION: Data suggest a role of the potassium channel SK3 (KCNN3 gene) in oxaliplatin-induced neurotoxicity (OIN). Length variations in the polymorphic CAG repeat of the KCNN3 gene may be associated with the risk of OIN. MATERIALS AND METHODS: We performed patch-clamp experiments on HEK293 cell lines, expressing SK3 channel isoforms with short (11) or long (24) CAG repetitions, to measure intracellular calcium concentrations to test the effects of oxaliplatin on current density...
May 17, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29765331/high-ph-sensitive-store-operated-ca-2-entry-mediated-by-ca-2-release-activated-ca-2-channels-in-rat-odontoblasts
#4
Maki Kimura, Koichi Nishi, Asuka Higashikawa, Sadao Ohyama, Kaoru Sakurai, Masakazu Tazaki, Yoshiyuki Shibukawa
Odontoblasts play a crucial role in dentin formation and sensory transduction following the application of stimuli to the dentin surface. Various exogenous and endogenous stimuli elicit an increase in the intracellular free calcium concentration ([Ca2+ ]i ) in odontoblasts, which is mediated by Ca2+ release from intracellular Ca2+ stores and/or Ca2+ influx from the extracellular medium. In a previous study, we demonstrated that the depletion of Ca2+ stores in odontoblasts activated store-operated Ca2+ entry (SOCE), a Ca2+ influx pathway...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29760086/mapping-the-functional-anatomy-of-orai1-transmembrane-domains-for-crac-channel-gating
#5
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
https://www.readbyqxmd.com/read/29758025/clca2-is-a-positive-regulator-of-store-operated-calcium-entry-and-tmem16a
#6
Aarushi Sharma, Grace Ramena, Yufang Yin, Louis Premkumar, Randolph C Elble
The Chloride Channel Accessory (CLCA) protein family was first characterized as regulators of calcium-activated chloride channel (CaCC) currents (ICaCC), but the mechanism has not been fully established. We hypothesized that CLCAs might regulate ICaCC by modulating intracellular calcium levels. In cells stably expressing human CLCA2 or vector, we found by calcium imaging that CLCA2 moderately enhanced intracellular-store release but dramatically increased store-operated entry of calcium upon cytosolic depletion...
2018: PloS One
https://www.readbyqxmd.com/read/29734114/the-early-signaling-pathway-of-live-yeast-cell-derivative-in-thp-1-monocytes
#7
Eric I Gruenstein, Donna J Schlemm, Mridula Bethi, Stephen J Keller
Live yeast cell derivative (LYCD) is a medicinal yeast extract that has been used in the treatment of burns, wounds and hemorrhoids for over 70 years. It has been shown to enhance the closure of skin wounds in diabetic mice by increasing inflammation, angiogenesis, formation of granulation tissue and epithelial migration. An active fraction of LYCD has been identified as a mixture of peptides ranging in size from 5 kDA to 17 kDA. Despite its widespread use over many years, understanding of the mechanism by which LYCD acts to effect tissue repair responses is very limited...
April 22, 2018: Cell Calcium
https://www.readbyqxmd.com/read/29726814/structure-of-the-human-lipid-gated-cation-channel-trpc3
#8
Chen Fan, Wooyoung Choi, Weinan Sun, Juan Du, Wei Lu
The TRPC channels are crucially involved in store-operated calcium entry and calcium homeostasis, and they are implicated in human diseases such as neurodegenerative disease, cardiac hypertrophy, and spinocerebellar ataxia. We present a structure of the full-length human TRPC3, a lipid-gated TRPC member, in a lipid-occupied, closed state at 3.3 Angstrom. TRPC3 has four elbow-like membrane reentrant helices prior to the first transmembrane helix. The TRP helix is perpendicular to, and thus disengaged from, the pore-lining S6, suggesting a different gating mechanism from other TRP subfamily channels...
May 4, 2018: ELife
https://www.readbyqxmd.com/read/29717981/electron-cryo-microscopy-structure-of-the-canonical-trpc4-ion-channel
#9
Deivanayagabarathy Vinayagam, Thomas Mager, Amir Apelbaum, Arne Bothe, Felipe Merino, Oliver Hofnagel, Christos Gatsogiannis, Stefan Raunser
Canonical transient receptor channels (TRPC) are non-selective cation channels. They are involved in receptor-operated Ca2+ signaling and have been proposed to act as store-operated channels (SOC). Their malfunction is related to cardiomyopathies and their modulation by small molecules has been shown to be effective against renal cancer cells. The molecular mechanism underlying the complex activation and regulation is poorly understood. Here, we report the electron cryo-microscopy structure of zebrafish TRPC4 in its unliganded (apo), closed state at an overall resolution of 3...
May 2, 2018: ELife
https://www.readbyqxmd.com/read/29712850/distinct-gating-mechanism-of-soc-channel-involving-stim-orai-coupling-and-an-intramolecular-interaction-of-orai-in-caenorhabditis-elegans
#10
Kyu Min Kim, Tharaka Wijerathne, Jin-Hoe Hur, Uk Jung Kang, Ihn Hyeong Kim, Yeong Cheon Kweon, Ah Reum Lee, Su Ji Jeong, Sang Kwon Lee, Yoon Young Lee, Bo-Woong Sim, Jong-Hee Lee, Chunggi Baig, Sun-Uk Kim, Kyu-Tae Chang, Kyu Pil Lee, Chan Young Park
Store-operated calcium entry (SOCE), an important mechanism of Ca2+ signaling in a wide range of cell types, is mediated by stromal interaction molecule (STIM), which senses the depletion of endoplasmic reticulum Ca2+ stores and binds and activates Orai channels in the plasma membrane. This inside-out mechanism of Ca2+ signaling raises an interesting question about the evolution of SOCE: How did these two proteins existing in different cellular compartments evolve to interact with each other? We investigated the gating mechanism of Caenorhabditis elegans Orai channels...
April 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29705161/ca-2-entry-through-reverse-mode-na-ca-2-exchanger-contributes-to-store-operated-channel-mediated-neointima-formation-after-arterial-injury
#11
Bei Liu, Bin Zhang, Shiliang Huang, Lixia Yang, Carolyn M Roos, Michael A Thompson, Y S Prakash, Jie Zang, Jordan D Miller, Ruiwei Guo
BACKGROUND: Na+ /Ca2+ exchange (NCX) reversal-mediated Ca2+ entry is a critical pathway for stimulating proliferation in many cell lines. However, the role of reverse-mode NCX1 in neointima formation and atherosclerosis remains unclear. The aims of the present study were to investigate the functional role of NCX1 in the pathogenesis of atherosclerosis and vascular smooth muscle cell (VSMC) proliferation, and to determine the interaction between NCX1 and store depletion in VSMCs. METHODS: A rat balloon injury model was established to examine the effect of the knockdown of NCX1 on neointima formation after injury...
January 31, 2018: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/29705071/s-nitrosylation-of-stim1-by-neuronal-nitric-oxide-synthase-inhibits-store-operated-ca-2-entry
#12
Le Gui, Jinhui Zhu, Xiangru Lu, Stephen M Sims, Wei-Yang Lu, Peter B Stathopulos, Qingping Feng
Store-operated Ca2+ entry (SOCE) mediated by stromal interacting molecule-1 (STIM1) and Orai1 represents a major route of Ca2+ entry in mammalian cells and is initiated by STIM1 oligomerization in the endoplasmic or sarcoplasmic reticulum (ER/SR). However, the effects of nitric oxide (NO) on STIM1 function are unknown. Neuronal NO synthase (nNOS) is located in the SR of cardiomyocytes. Here, we show that STIM1 is susceptible to S-nitrosylation. nNOS deficiency or inhibition enhanced Ca2+ release-activated Ca2+ channel current (ICRAC ) and SOCE in cardiomyocytes...
April 26, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29693611/smart-system-for-bicarbonate-control-in-irrigation-for-hydroponic-precision-farming
#13
Carlos Cambra, Sandra Sendra, Jaime Lloret, Raquel Lacuesta
Improving the sustainability in agriculture is nowadays an important challenge. The automation of irrigation processes via low-cost sensors can to spread technological advances in a sector very influenced by economical costs. This article presents an auto-calibrated pH sensor able to detect and adjust the imbalances in the pH levels of the nutrient solution used in hydroponic agriculture. The sensor is composed by a pH probe and a set of micropumps that sequentially pour the different liquid solutions to maintain the sensor calibration and the water samples from the channels that contain the nutrient solution...
April 25, 2018: Sensors
https://www.readbyqxmd.com/read/29677491/the-allergen-der-p3-from-house-dust-mite-stimulates-store-operated-ca-2-channels-and-mast-cell-migration-through-par4-receptors
#14
Yu-Ping Lin, Charmaine Nelson, Holger Kramer, Anant B Parekh
The house dust mite is the principal source of perennial aeroallergens in man. How these allergens activate innate and adaptive immunity is unclear, and therefore, there are no therapies targeting mite allergens. Here, we show that house dust mite extract activates store-operated Ca2+ channels, a common signaling module in numerous cell types in the lung. Activation of channel pore-forming Orai1 subunits by mite extract requires gating by STIM1 proteins. Although mite extract stimulates both protease-activated receptor type 2 (PAR2) and PAR4 receptors, Ca2+ influx is more tightly coupled to the PAR4 pathway...
April 19, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29669320/camkii-potentiates-store-operated-ca2-entry-through-enhancing-stim1-aggregation-and-interaction-with-orai1
#15
Shu Li, Jingyi Xue, Zhipeng Sun, Tiantian Liu, Lane Zhang, Limin Wang, Hongjie You, Zheng Fan, Yuanyuan Zheng, Dali Luo
BACKGROUND/AIMS: Upon Ca2+ store depletion, stromal interaction molecule 1 (STIM1) oligomerizes, redistributes near plasmalemma to interact with Ca2+ selective channel-forming subunit (Orai1) and initiates store-operated Ca2+ entry (SOCE). Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a regulator of SOCE, but how CaMKII regulates SOCE remains obscure. METHODS: Using Fura2, confocal microscopy, co-immunoprecipitation, specific blocker and overexpression/knockdown approaches, we evaluated STIM1 aggregation and its interaction with Orai1, and SOCE upon Ca2+ store depletion in thapsigargin (TG) treated HEK293 and HeLa cells...
April 13, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29661937/a-charge-sensing-region-in-the-stromal-interaction-molecule-1-luminal-domain-confers-stabilization-mediated-inhibition-of-soce-in-response-to-s-nitrosylation
#16
Jinhui Zhu, Xiangru Lu, Qingping Feng, Peter B Stathopulos
Store-operated calcium (Ca2+ ) entry (SOCE) is a major Ca2+ signaling pathway facilitating extracellular Ca2+ influx in response to the initial release of intracellular endo/sarcoplasmic reticulum (ER/SR) Ca2+ stores. Stromal interaction molecule-1 (STIM1) is the Ca2+ sensor which activates SOCE following ER/SR Ca2+ depletion. The EF-hand together with the adjacent sterile α motif (EFSAM) domains of STIM1 are essential for detecting changes in luminal Ca2+ concentrations. Low ER Ca2+ levels trigger STIM1 destabilization and oligomerization, culminating in the opening of Orai1-composed Ca2+ channels on the plasma membrane...
April 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29628897/stanniocalcin-2-regulates-non-capacitative-ca-2-entry-and-aggregation-in-mouse-platelets
#17
Esther López, L Gómez-Gordo, Carlos Cantonero, Nuria Bermejo, Jorge Pérez-Gómez, María P Granados, Gines M Salido, Juan A Rosado Dionisio, Pedro C Redondo Liberal
Stanniocalcin 2 (STC2) is a fish protein that controls body Ca2+ and phosphate metabolism. STC2 has also been described in mammals, and as platelet function highly depends on both extracellular and intracellular Ca2+ , we have explored its expression and function in these cells. STC2-/- mice exhibit shorter tail bleeding time than WT mice. Platelets from STC2-deficient mice showed enhanced aggregation, as well as enhanced Ca2+ mobilization in response to the physiological agonist thrombin (Thr) and the diacylglycerol analog, OAG, a selective activator of the non-capacitative Ca2+ entry channels...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29623030/on-the-role-of-store-operated-calcium-entry-in-acute-and-chronic-neurodegenerative-diseases
#18
REVIEW
Agnese Secondo, Giacinto Bagetta, Diana Amantea
In both excitable and non-excitable cells, calcium (Ca2+ ) signals are maintained by a highly integrated process involving store-operated Ca2+ entry (SOCE), namely the opening of plasma membrane (PM) Ca2+ channels following the release of Ca2+ from intracellular stores. Upon depletion of Ca2+ store, the stromal interaction molecule (STIM) senses Ca2+ level reduction and migrates from endoplasmic reticulum (ER)-like sites to the PM where it activates the channel proteins Orai and/or the transient receptor potential channels (TRPC) prompting Ca2+ refilling...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29618985/the-complex-role-of-store-operated-calcium-entry-pathways-and-related-proteins-in-the-function-of-cardiac-skeletal-and-vascular-smooth-muscle-cells
#19
REVIEW
Javier Avila-Medina, Isabel Mayoral-Gonzalez, Alejandro Dominguez-Rodriguez, Isabel Gallardo-Castillo, Juan Ribas, Antonio Ordoñez, Juan A Rosado, Tarik Smani
Cardiac, skeletal, and smooth muscle cells shared the common feature of contraction in response to different stimuli. Agonist-induced muscle's contraction is triggered by a cytosolic free Ca2+ concentration increase due to a rapid Ca2+ release from intracellular stores and a transmembrane Ca2+ influx, mainly through L-type Ca2+ channels. Compelling evidences have demonstrated that Ca2+ might also enter through other cationic channels such as Store-Operated Ca2+ Channels (SOCCs), involved in several physiological functions and pathological conditions...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29604968/a-critical-appraisal-of-the-role-of-intracellular-ca-2-signaling-pathways-in-kawasaki-disease
#20
REVIEW
Jeroen Bijnens, Ludwig Missiaen, Geert Bultynck, Jan B Parys
Kawasaki disease is a multi-systemic vasculitis that generally occurs in children and that can lead to coronary artery lesions. Recent studies showed that Kawasaki disease has an important genetic component. In this review, we discuss the single-nucleotide polymorphisms in the genes encoding proteins with a role in intracellular Ca2+ signaling: inositol 1,4,5-trisphosphate 3-kinase C, caspase-3, the store-operated Ca2+ -entry channel ORAI1, the type-3 inositol 1,4,5-trisphosphate receptor, the Na+ /Ca2+ exchanger 1, and phospholipase Cß4 and Cß1...
May 2018: Cell Calcium
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