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https://www.readbyqxmd.com/read/28319095/rcn1-suppresses-er-stress-induced-apoptosis-via-calcium-homeostasis-and-perk-chop-signaling
#1
S Xu, Y Xu, L Chen, Q Fang, S Song, J Chen, J Teng
Endoplasmic reticulum (ER) stress is caused by the disturbance of ER homeostasis and leads to the activation of the unfolded protein response (UPR), which alleviates stress at an early stage and triggers apoptosis if homeostasis fails over a prolonged timeframe. Here, we report that reticulocalbin 1 (RCN1), a member of the CREC family, is transactivated by nuclear factor kappa B (NF-κB) during ER stress and inhibits ER stress-induced apoptosis. The depletion of RCN1 increases the UPR during drug-induced ER stress by activating PRKR-like ER kinase-CCAAT/enhancer-binding protein-homologous protein (PERK-CHOP) signaling, thus inducing apoptosis...
March 20, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28318884/udp-p2y6-receptor-signaling-regulates-ige-dependent-degranulation-in-human-basophils
#2
Manabu Nakano, Koichi Ito, Takeo Yuno, Nobuyuki Soma, Syun Aburakawa, Kosuke Kasai, Toshiya Nakamura, Hideki Takami
BACKGROUND: P2Y purinergic receptors (P2YR) are G protein-coupled receptors that are stimulated by extracellular nucleotides. They mediate cellular effects by regulating cAMP production, protein kinase C activation, inositol trisphosphate generation, and Ca(2+) release from intracellular stores. The P2Y6 receptor of this family is selectively stimulated by UDP, and selectively inhibited by MRS2578. In the present study, we examined the effect of UDP/P2Y6 receptor signaling on IgE-dependent degranulation in human basophils...
March 16, 2017: Allergology International: Official Journal of the Japanese Society of Allergology
https://www.readbyqxmd.com/read/28317879/a-novel-method-for-screening-adenosine-receptor-specific-agonists-for-use-in-adenosine-drug-development
#3
Karlie R Jones, Uimook Choi, Ji-Liang Gao, Robert D Thompson, Larry E Rodman, Harry L Malech, Elizabeth M Kang
Agonists that target the A1, A2A, A2B and A3 adenosine receptors have potential to be potent treatment options for a number of diseases, including autoimmune diseases, cardiovascular disease and cancer. Because each of these adenosine receptors plays a distinct role throughout the body, obtaining highly specific receptor agonists is essential. Of these receptors, the adenosine A2AR and A2BR share many sequence and structural similarities but highly differ in their responses to inflammatory stimuli. Our laboratory, using a combination of specially developed cell lines and calcium release analysis hardware, has created a new and faster method for determining specificity of synthetic adenosine agonist compounds for the A2A and A2B receptors in human cells...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28317338/release-of-calcium-into-the-myofibrillar-space-in-response-to-active-shortening-of-striated-muscle
#4
K A P Edman, C Caputo
AIM: The study was undertaken to explore whether shortening of striated muscle during activity is associated with release of bound Ca(2+) into the myofibrillar space as has previously been proposed in order to explain the depressant effect of active shortening. METHODS: The experiments were carried out on single muscle fibres isolated from the anterior tibialis muscle of Rana temporaria. The fibres were loaded with the calcium sensitive indicator Fluo-3. The fibres, stimulated to produce a partially fused isometric tetanus, were subjected to a shortening ramp or, alternatively, to a stretch ramp during activity while force, fibre length, sarcomere length and the Fluo-3 signal were recorded...
March 19, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28316920/measurement-of-ph-and-calcium-ions-release-from-different-calcium-hydroxide-pastes-at-different-intervals-of-time-atomic-spectrophotometric-analysis
#5
Pranab Misra, Rhythm Bains, Kapil Loomba, Abhinav Singh, V P Sharma, R C Murthy, Rakesh Kumar
AIM: To evaluate the effect of different vehicles on pH and release of calcium ions from calcium hydroxide (CH) paste from apical third of root canals. METHODS: 40 single rooted extracted human mandibular premolars were instrumented with RevoS files (MicroMega) up to ISO size 40. The teeth were divided into 4 groups on the basis of vehicle as follows: Group I - calcium hydroxide mixed with 2% chlorhexidine; Group II - calcium hydroxide mixed with propylene glycol; Group III - calcium hydroxide mixed with glycerine; and Control - calcium hydroxide mixed with double distilled water...
January 2017: Journal of Oral Biology and Craniofacial Research
https://www.readbyqxmd.com/read/28315072/direct-myosin-activation-by-omecamtiv-mecarbil-for-heart-failure-with-reduced-ejection-fraction
#6
Mitchell A Psotka, John R Teerlink
Myosin is the indispensable molecular motor that utilizes chemical energy to produce force for contraction within the cardiac myocyte. Myosin activity is gated by intracellular calcium levels which are regulated by multiple upstream signaling cascades that can be altered for clinical utility using inotropic medications. In contrast to clinically available cardiac inotropes, omecamtiv mecarbil is a novel direct myosin activator developed to augment left ventricular systolic function without the undesirable secondary effects of altered calcium homeostasis...
March 18, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28314317/statins-protect-against-acute-rt-related-rectal-toxicity-in-patients-with-prostate-cancer-an-observational-prospective-study
#7
Isabella Palumbo, Fabio Matrone, Giampaolo Montesi, Rita Bellavita, Marco Lupattelli, Simonetta Saldi, Alessandro Frattegiani, Eleonora Arena, Cristina Mariucci, Lorenzo Falcinelli, Vittorio Bini, Cynthia Aristei
AIM: To analyze risk factors for acute rectal toxicity during hypofractionated intensity-modulated radiotherapy (IMRT) for prostate cancer. PATIENTS AND METHODS: A total of 195 patients received 74.25 Gy in 33 fractions to the prostate and, if involved, to the seminal vescicles (SV). When the risk of SV involvement was >15% according to the Roach's formula, they received 62 Gy in 33 fractions. Overall, 107/195 patients (54.87%) received hormonal therapy (luteinizing hormone-releasing hormone analogue, anti-androgen, or both)...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28314177/gintonin-attenuates-depressive-like-behaviors-associated-with-alcohol-withdrawal-in-mice
#8
Hyeon-Joong Kim, Sang-Deuk Park, Ra Mi Lee, Byung-Hwan Lee, Sun-Hye Choi, Sung-Hee Hwang, Hyewhon Rhim, Hyoung-Chun Kim, Seung-Yeol Nah
BACKGROUND: Panax ginseng Meyer extracts have been used to improve mood and alleviate symptoms of depression. However, little is known about the extracts' active ingredients and the molecular mechanisms underlying their reported anti-depressive effects. METHODS: Gintonin is an exogenous lysophosphatidic acid (LPA) receptor ligand isolated from P. ginseng. BON cells, an enterochromaffin cell line, and C57BL/6 mice were used to investigate whether gintonin stimulates serotonin release...
March 9, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/28306606/spinal-microglial-p2x4-receptor-brain-derived-neurotrophic-factor-signaling-regulates-nicotine-withdrawal-induced-hyperalgesia
#9
Xiaodi Zhang, Pengcheng Xu, Chengbao Li, Wenchao Zhu, Shanshan Wu, Ailan Yu, Yonghong Ding, Qinghe Wang, Zongwang Zhang
Nicotine withdrawal (NTW) has been shown to increase pain sensitivity. However, the pathogenesis of NTW-induced hyperalgesia syndrome is unknown. Microglial activation, with increased expression of the P2X4 receptor (P2X4R) and brain-derived neurotrophic factor (BDNF) as important markers, is associated with hyperalgesia; therefore, these markers may represent an unprecedented target to prevent hyperalgesia. In this study, we explored the contributions of spinal microglial P2X4R-BDNF signaling in NTW-induced hyperalgesia...
March 16, 2017: Neuroreport
https://www.readbyqxmd.com/read/28306255/development-of-potent-and-selective-antagonists-for-the-utp-activated-p2y4-receptor
#10
Muhammad Rafehi, Enas Malik, Alexander Neumann, Aliaa Abdelrahman, Theodor Hanck, Vigneshwaran Namasivayam, Christa E Müller, Younis Baqi
P2Y4 is a Gq protein-coupled receptor activated by uridine-5'-triphosphate (UTP), which is widely expressed in the body, e.g., in intestine, heart, and brain. No selective P2Y4 receptor antagonist has been described so far. Therefore, we developed and optimized P2Y4 antagonists based on an anthraquinone scaffold. Potency was assessed by a fluorescence-based assay measuring inhibition of UTP-induced intracellular calcium release in 1321N1 astrocytoma cells stably transfected with the human P2Y4 receptor. The most potent compound of the present series, sodium 1-amino-4-[4-(2,4-dimethylphenylthio)phenylamino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (PSB-16133, 61) exhibited an IC50 value of 233 nM, selectivity versus other P2Y receptor subtypes, and is thought to act as an allosteric antagonist...
March 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28304022/altering-the-level-of-calcium-changes-the-physical-properties-and-digestibility-of-casein-based-emulsion-gels
#11
Irene McIntyre, Michael O Sullivan, Dolores O Riordan
Casein-based emulsion gels prepared with different types of lipid (i.e. milk fat or rapeseed oil) were formulated with high (774 mg Ca per 100 g) or low (357 mg Ca per 100 g) calcium levels by blending acid and rennet casein. Their physicochemical characteristics (i.e. composition, texture, microstructure & water mobility) and in vitro digestibility were compared to conventionally formulated high-calcium (723 mg Ca per 100 g) emulsion gels made from rennet casein with calcium chelating salts (CCS). CCS-free, high-calcium emulsion gels were significantly (p ≤ 0...
March 17, 2017: Food & Function
https://www.readbyqxmd.com/read/28303961/the-metabolic-waste-ammonium-regulates-mtorc2-and-mtorc1-signaling
#12
Ahmad Merhi, Paul Delrée, Anna Maria Marini
Two structurally and functionally distinct mammalian TOR complexes control cell growth and metabolism in physiological and pathological contexts including cancer. Upregulated glutaminolysis is part of the metabolic reprogramming occurring in cancer, providing fuels for growth but also liberating ammonium, a potent neurotoxic waste product. Here, we identify ammonium as a novel dose-dependent signal mediating rapid mTORC2 activation and further regulating mTORC1. We show that ammonium induces rapid RICTOR-dependent phosphorylation of AKT-S473, a process requiring the PI3K pathway and further involving the Src-family kinase YES1, the FAK kinase and the ITGβ1 integrin...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28303572/intracellular-calcium-release-channels-an-update
#13
Gaetano Santulli, Ryutaro Nakashima, Qi Yuan, Andrew R Marks
Ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP3Rs) are calcium (Ca(2+) ) release channels on the endo/sarcoplasmic reticulum (ER/SR). Here we summarize the latest advances in the field, describing the recently discovered mechanistic roles of intracellular Ca(2+) release channels in the regulation of mitochondrial fitness and endothelial function, providing novel therapeutic options for the treatment of heart failure, hypertension, and diabetes mellitus. This article is protected by copyright...
March 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28301019/cytotoxicity-of-new-calcium-aluminate-cement-endobinder-containing-different-radiopacifiers
#14
Claudia Huck, Hernane da Silva Barud, Fernanda Gonçalves Basso, Carlos Alberto de Souza Costa, Josimeri Hebling, Lucas da Fonseca Roberti Garcia
This study aimed to evaluate the cytotoxicity of a calcium aluminate cement (EndoBinder) containing different radiopacifiers, Bi2O3, ZnO or ZrO2, compared with Mineral Trioxide Aggregate (MTA). According to ISO 10993-12:2012 (E) recommendations, 0.2 g of each cement were applied in transwell inserts and placed in 24-well culture plates containing 1 mL of culture medium (DMEM). After 24 h of incubation, the extracts (DMEM containing components released from the cements) were applied to immortalized odontoblast-like MDPC-23 cells...
January 2017: Brazilian Dental Journal
https://www.readbyqxmd.com/read/28299842/electroacupuncture-promotes-cns-dependent-release-of-mesenchymal-stem-cells
#15
Tatiana E Salazar, Matthew R Richardson, Eleni Beli, Matthew S Ripsch, John George, Youngsook Kim, Yaqian Duan, Leni Moldovan, Yuanqing Yan, Ashay Bhatwadekar, Vaishnavi Jadhav, Jared A Smith, Susan McGorray, Alicia L Bertone, Dmitri O Traktuev, Keith L March, Luis M Colon-Perez, Keith Avin, Emily Sims, Julie A Mund, Jamie Case, Shaolin Deng, Min Su Kim, Bruce McDavitt, Michael E Boulton, Jeffrey Thinschmidt, Sergio Li Calzi, Stephanie D Fitz, Robyn K Fuchs, Stuart J Warden, Todd McKinley, Anantha Shekhar, Marcelo Febo, Phillip L Johnson, Lung Ji Chang, Zhanguo Gao, Mikhail G Kolonin, Song Lai, Jinfeng Ma, Xinzhong Dong, Fletcher A White, Huisheng Xie, Mervin C Yoder, Maria B Grant
Electro-acupuncture (EA) performed in rats and humans using front-limb acupuncture sites, LI-4 and LI-11, and Du-14 and Du-20 increased functional connectivity between the anterior hypothalamus and the amygdala and mobilized mesenchymal stem cells (MSC) into the systemic circulation. In human subjects, the source of the MSC was found to be primarily adipose tissue whereas in rodents the tissue sources were considered more heterogeneous. Pharmacological disinhibition of rat hypothalamus enhanced sympathetic nervous system (SNS) activation and similarly resulted in a release of MSC into the circulation...
March 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/28298360/stimulation-of-fibroblast-growth-factor-23-by-metabolic-acidosis-requires-osteoblastic-intracellular-calcium-signaling-and-prostaglandin-synthesis
#16
Nancy S Krieger, David A Bushinsky
Serum fibroblast growth factor 23 (FGF23) increases progressively in chronic kidney disease (CKD) and is associated with increased mortality. FGF23 is synthesized in osteoblasts and osteocytes; however, the factors regulating its production are not clear. Patients with CKD have decreased renal acid excretion leading to metabolic acidosis (MET). During MET, acid is buffered by bone with release of mineral calcium (Ca) and phosphate (P). MET increases intracellular Ca signaling and cyclooxygenase 2 (COX2)-induced prostaglandin production in the osteoblast leading to decreased bone formation and increased bone resorption...
March 15, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28298333/multiple-ampk-activators-inhibit-l-carnitine-uptake-in-c2c12-skeletal-muscle-myotubes
#17
Andy Shaw, Stewart Jeromson, Kenneth R Watterson, John D Pediani, Iain Gallagher, Tim Whalley, Gillian Dreczkowski, Naomi Brooks, Stuart Galloway, D Lee Hamilton
Mutations in the gene that encodes the principal L-Carnitine transporter, OCTN2, can lead to a reduced intracellular L-Carnitine pool and the disease Primary Carnitine Deficiency. L-Carnitine supplementation is used therapeutically to increase intracellular L-Carnitine. As AMPK and insulin regulate fat metabolism and substrate uptake we hypothesised that AMPK activating compounds and insulin would increase L-Carnitine uptake in C2C12 myotubes. The cells express all three OCTN transporters at the mRNA level and immunohistochemistry confirmed expression at the protein level...
March 15, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28297674/nanoscale-structural-plasticity-of-the-active-zone-matrix-modulates-presynaptic-function
#18
Oleg O Glebov, Rachel E Jackson, Christian M Winterflood, Dylan M Owen, Ellen A Barker, Patrick Doherty, Helge Ewers, Juan Burrone
The active zone (AZ) matrix of presynaptic terminals coordinates the recruitment of voltage-gated calcium channels (VGCCs) and synaptic vesicles to orchestrate neurotransmitter release. However, the spatial organization of the AZ and how it controls vesicle fusion remain poorly understood. Here, we employ super-resolution microscopy and ratiometric imaging to visualize the AZ structure on the nanoscale, revealing segregation between the AZ matrix, VGCCs, and putative release sites. Long-term blockade of neuronal activity leads to reversible AZ matrix unclustering and presynaptic actin depolymerization, allowing for enrichment of AZ machinery...
March 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28295108/porous-calcium-carbonate-as-a-carrier-material-to-increase-the-dissolution-rate-of-poorly-soluble-flavouring-compounds
#19
Maria Lundin Johnson, David Noreland, Patrick Gane, Joachim Schoelkopf, Cathy Ridgway, Anna Millqvist Fureby
Two different food grade functionalised porous calcium carbonates (FCC), with different pore size and pore size distributions, were characterised and used as carrier materials to increase the dissolution rate of poorly soluble flavouring compounds in aqueous solution. The loading level was varied between 1.3% by weight (wt%) and 35 wt%, where the upper limit of 35 wt% was the total maximum loading capacity of flavouring compound in FCC based on the fraction of the total weight of FCC plus flavouring compound...
March 15, 2017: Food & Function
https://www.readbyqxmd.com/read/28294127/orai2-modulates-store-operated-calcium-entry-and-t-cell-mediated-immunity
#20
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
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