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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
#1
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/28633902/calcium-sensing-receptor-initiating-cystathionine-gamma-lyase-hydrogen-sulfide-pathway-to-inhibit-platelet-activation-in-hyperhomocysteinemia-rat
#2
Yuwen Wang, Ziqing Zhao, Sa Shi, Fei Gao, Jichao Wu, Shiyun Dong, Weihua Zhang, Yanhong Liu, Xin Zhong
Hyperhomocysteinemia (HHcy, high homocysteine) induces the injury of endothelial cells (ECs). Hydrogen sulfide (H2S) protects ECs and inhibits the activation of platelets. Calcium-sensing receptor (CaSR) regulates the production of endogenous H2S. However, whether CaSR inhibits the injury of ECs and the activation of platelets by regulating the endogenous cystathionine-gamma-lyase (CSE, a major enzyme that produces H2S)/H2S pathway in hyperhomocysteinemia has not been previously investigated. Here, we tested the ultrastructure alterations of ECs and platelets, the changes in the concentration of serum homocysteine and the parameters of blood of hyperhomocysteinemia rats were measured...
June 19, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28629579/role-of-soce-architects-stim-and-orai-proteins-in-cell-death
#3
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/28623807/hiv-tat-excites-d1-receptor-like-expressing-neurons-from-rat-nucleus-accumbens
#4
G Cristina Brailoiu, Elena Deliu, Jeffrey L Barr, Linda M Console-Bram, Alexandra M Ciuciu, Mary E Abood, Ellen M Unterwald, Eugen Brailoiu
BACKGROUND: HIV-1 infection and drug abuse are frequently co-morbid and their association greatly increases the severity of HIV-1-induced neuropathology. While nucleus accumbens (NAcc) function is severely perturbed by drugs of abuse, little is known about how HIV-1 infection affects NAcc. METHODS: We used calcium and voltage imaging to investigate the effect of HIV-1 trans-activator of transcription (Tat) on rat NAcc. Based on previous neuronal studies, we hypothesized that Tat modulates intracellular Ca(2+) homeostasis of NAcc neurons...
June 8, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28620721/a-novel-gain-of-function-mutation-in-the-itpr1-suppressor-domain-causes-spinocerebellar-ataxia-with-altered-ca-2-signal-patterns
#5
Jillian P Casey, Taisei Hirouchi, Chihiro Hisatsune, Bryan Lynch, Raymond Murphy, Aimee M Dunne, Akitoshi Miyamoto, Sean Ennis, Nick van der Spek, Bronagh O'Hici, Katsuhiko Mikoshiba, Sally Ann Lynch
We report three affected members, a mother and her two children, of a non-consanguineous Irish family who presented with a suspected autosomal dominant spinocerebellar ataxia characterized by early motor delay, poor coordination, gait ataxia, and dysarthria. Whole exome sequencing identified a novel missense variant (c.106C>T; p.[Arg36Cys]) in the suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor gene (ITPR1) as the cause of the disorder, resulting in a molecular diagnosis of spinocerebellar ataxia type 29...
June 15, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28619002/targeting-astrocytes-for-treatment-in-amyotrophic-lateral-sclerosis
#6
Mina Perić, Dinko Mitrečić, Pavle R Andjus
Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder affecting upper and lower motoneurons. The two types, sporadic and familial differ in the aetiopathogenesis but have a similar neuropathology characterized by oxidative stress, excitotoxicity and inflammation. The disease is also characterized by a non-cell autonomous mechanism with astrocytes playing a central role by affecting synaptic glutamate, the blood-brain barrier, and metabolic and trophic support. Two types of therapeutic approaches focusing on astrocytes are presented: a) emerging molecular targets (potassium inward rectifier channels and aquaporins at the astrocyte endfeet, and IP3 receptor signaling pathway), and b) cell therapy with stem cell - generated and transplanted astrocytes...
June 15, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28615414/loss-of-ip3-receptor-mediated-ca-2-release-in-mouse-b-cells-results-in-abnormal-b-cell-development-and-function
#7
Huayuan Tang, Hong Wang, Qingsong Lin, Feifei Fan, Fei Zhang, Xiaohong Peng, Xi Fang, Jie Liu, Kunfu Ouyang
Intracellular calcium (Ca(2+)) mobilization after engagement of the BCR has been proposed to play an important role in B cell development and function. BCR activation causes an initial Ca(2+) release from the endoplasmic reticulum that is mediated by inositol 1,4,5-trisphosphate receptor (IP3R) and then triggers store-operated Ca(2+) entry once endoplasmic reticulum Ca(2+) store is depleted. Store-operated Ca(2+) entry has been shown to regulate B cell function but is dispensable for B cell development. By contrast, the function of IP3R-mediated Ca(2+) release in B cells remains to be determined...
June 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28615319/retinoschisin-is-linked-to-retinal-na-k-atpase-signaling-and-localization
#8
Karolina Plössl, Melanie Royer, Sarah Bernklau, Neslihan N Tavraz, Thomas Friedrich, Jens Wild, Bernhard H F Weber, Ulrike Friedrich
Mutations in the RS1 gene cause X-linked juvenile retinoschisis (XLRS), a hereditary retinal dystrophy. We have recently shown that retinoschisin, the protein encoded by RS1, regulates ERK signaling and apoptosis in retinal cells. In this study, we explored an influence of retinoschisin on the functionality of the Na/K-ATPase, its interaction partner at retinal plasma membranes. We show that retinoschisin binding requires the β2-subunit of the Na/K-ATPase while the α-subunit is exchangeable. Our investigations revealed no impact of retinoschisin on Na/K-ATPase mediated ATP hydrolysis and ion transport...
June 14, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28614300/pten-counteracts-fbxl2-to-promote-ip3r3-and-ca-2-mediated-apoptosis-limiting-tumour-growth
#9
Shafi Kuchay, Carlotta Giorgi, Daniele Simoneschi, Julia Pagan, Sonia Missiroli, Anita Saraf, Laurence Florens, Michael P Washburn, Ana Collazo-Lorduy, Mireia Castillo-Martin, Carlos Cordon-Cardo, Said M Sebti, Paolo Pinton, Michele Pagano
In response to environmental cues that promote IP3 (inositol 1,4,5-trisphosphate) generation, IP3 receptors (IP3Rs) located on the endoplasmic reticulum allow the 'quasisynaptical' feeding of calcium to the mitochondria to promote oxidative phosphorylation. However, persistent Ca(2+) release results in mitochondrial Ca(2+) overload and consequent apoptosis. Among the three mammalian IP3Rs, IP3R3 appears to be the major player in Ca(2+)-dependent apoptosis. Here we show that the F-box protein FBXL2 (the receptor subunit of one of 69 human SCF (SKP1, CUL1, F-box protein) ubiquitin ligase complexes) binds IP3R3 and targets it for ubiquitin-, p97- and proteasome-mediated degradation to limit Ca(2+) influx into mitochondria...
June 14, 2017: Nature
https://www.readbyqxmd.com/read/28592421/clustering-of-ca-2-transients-in-interstitial-cells-of-cajal-defines-slow-wave-duration
#10
Bernard T Drumm, Grant W Hennig, Matthew J Battersby, Erin K Cunningham, Tae Sik Sung, Sean M Ward, Kenton M Sanders, Salah A Baker
Interstitial cells of Cajal (ICC) in the myenteric plexus region (ICC-MY) of the small intestine are pacemakers that generate rhythmic depolarizations known as slow waves. Slow waves depend on activation of Ca(2+)-activated Cl(-) channels (ANO1) in ICC, propagate actively within networks of ICC-MY, and conduct to smooth muscle cells where they generate action potentials and phasic contractions. Thus, mechanisms of Ca(2+) regulation in ICC are fundamental to the motor patterns of the bowel. Here, we characterize the nature of Ca(2+) transients in ICC-MY within intact muscles, using mice expressing a genetically encoded Ca(2+) sensor, GCaMP3, in ICC...
June 7, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28549333/endoplasmic-reticulum-er-stress-and-camp-pka-pathway-mediated-zn-induced-hepatic-lipolysis
#11
Yu-Feng Song, Christer Hogstrand, Chuan-Chuan Wei, Kun Wu, Ya-Xiong Pan, Zhi Luo
The present study was performed to determine the effect of Zn exposure influencing endoplasmic reticulum (ER) stress, explore the underlying molecular mechanism of Zn-induced hepatic lipolysis in a fish species of significance for aquaculture, yellow catfish Pelteobagrus fulvidraco. We found that waterborne Zn exposure evoked ER stress and unfolded protein response (UPR), and activated cAMP/PKA pathway, and up-regulated hepatic lipolysis. The increase in ER stress and lipolysis were associated with activation of cAMP/PKA signaling pathway...
May 23, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28538151/mapping-interpuff-interval-distribution-to-the-properties-of-inositol-trisphosphate-receptors
#12
Pengxing Cao, Martin Falcke, James Sneyd
Tightly clustered inositol trisphosphate receptors (IP3Rs) control localized Ca(2+) liberation from the endoplasmic reticulum to generate repetitive Ca(2+) puffs. Distributions of the interpuff interval (IPI), i.e., the waiting time between successive puffs, are found to be well characterized by a probability density function involving only two parameters, λ and ξ, which represent the basal rate of puff generation and the recovery rate from refractoriness, respectively. However, how the two parameters depend on the kinetic parameters of single IP3Rs in a cluster is still unclear...
May 23, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28526746/region-specific-proteolysis-differentially-regulates-type-1-inositol-1-4-5-trisphosphate-receptor-activity
#13
Liwei Wang, Larry E Wagner, Kamil J Alzayady, David I Yule
The inositol 1,4,5 trisphosphate receptor (IP3R) is an intracellular Ca2+ release channel expressed predominately on the membranes of the endoplasmic reticulum. IP3R1 can be cleaved by caspase or calpain into at least two receptor fragments. However, the functional consequences of receptor fragmentation are poorly understood. Our previous work has demonstrated that IP3R1 channels, formed following either enzymatic fragmentation or expression of the corresponding complementary polypeptide chains, retain tetrameric architecture and are still activated by IP3 binding, despite the loss of peptide continuity...
May 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28506928/distinct-phosphodiesterase-5a-containing-compartments-allow-selective-regulation-of-cgmp-dependent-signalling-in-human-arterial-smooth-muscle-cells
#14
Lindsay S Wilson, Manhong Guo, M Bibiana Umana, Donald H Maurice
Cyclic GMP (cGMP) translates and integrates much of the information encoded by nitric oxide (NO(·)) and several natriuretic peptides, including the atrial natriuretic peptide (ANP). Previously, we reported that integration of a cGMP-specific cyclic nucleotide phosphodiesterase, namely phosphodiesterase 5A (PDE5A), into a protein kinase G (PKG)- and inositol-1,4,5-trisphosphate receptor (IP3R)-containing endoplasmic reticulum (ER) signalosome allows localized control of PDE5A activity and of PKG-dependent inhibition of IP3-mediated release of ER Ca(2+) in human platelets...
May 12, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28506554/selective-dopamine-receptor-4-activation-mediates-the-hippocampal-neuronal-calcium-response-via-ip3-and-ryanodine-receptors
#15
Ya-Li Wang, Jian-Gang Wang, Fang-Li Guo, Xia-Huan Gao, Dan-Dan Zhao, Lin Zhang, Jian-Zhi Wang, Cheng-Biao Lu
Intracellular calcium is a key factor in most cellular processes, including cell growth, differentiation, proliferation and neurotransmitter release. Dopamine (DA) mediates synaptic transmission by regulating the intracellular calcium content. It is not clear, however, which specific subunit of the DA receptor contributes to DA modulation of intracellular calcium content changes. Through the traditional technique of Fura-2 calcium imaging, this study demonstrated that the DA can induce transient calcium in cultured hippocampal neurons and that this response can be mimicked by a selective dopamine receptor 4 (DR4) agonist PD168077 (PD)...
May 12, 2017: Brain Research
https://www.readbyqxmd.com/read/28504276/targeted-calcium-influx-boosts-cytotoxic-t-lymphocyte-function-in-the-tumour-microenvironment
#16
Kyun-Do Kim, Seyeon Bae, Tara Capece, Hristina Nedelkovska, Rafael G de Rubio, Alan V Smrcka, Chang-Duk Jun, Woojin Jung, Byeonghak Park, Tae-Il Kim, Minsoo Kim
Adoptive cell transfer utilizing tumour-targeting cytotoxic T lymphocytes (CTLs) is one of the most effective immunotherapies against haematological malignancies, but significant clinical success has not yet been achieved in solid tumours due in part to the strong immunosuppressive tumour microenvironment. Here, we show that suppression of CTL killing by CD4(+)CD25(+)Foxp3(+) regulatory T cell (Treg) is in part mediated by TGFβ-induced inhibition of inositol trisphosphate (IP3) production, leading to a decrease in T cell receptor (TCR)-dependent intracellular Ca(2+) response...
May 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28495747/reticulon-3-dependent-er-pm-contact-sites-control-egfr-nonclathrin-endocytosis
#17
Giusi Caldieri, Elisa Barbieri, Gilda Nappo, Andrea Raimondi, Massimo Bonora, Alexia Conte, Lisette G G C Verhoef, Stefano Confalonieri, Maria Grazia Malabarba, Fabrizio Bianchi, Alessandro Cuomo, Tiziana Bonaldi, Emanuele Martini, Davide Mazza, Paolo Pinton, Carlo Tacchetti, Simona Polo, Pier Paolo Di Fiore, Sara Sigismund
The integration of endocytic routes is critical to regulate receptor signaling. A nonclathrin endocytic (NCE) pathway of the epidermal growth factor receptor (EGFR) is activated at high ligand concentrations and targets receptors to degradation, attenuating signaling. Here we performed an unbiased molecular characterization of EGFR-NCE. We identified NCE-specific regulators, including the endoplasmic reticulum (ER)-resident protein reticulon 3 (RTN3) and a specific cargo, CD147. RTN3 was critical for EGFR/CD147-NCE, promoting the creation of plasma membrane (PM)-ER contact sites that were required for the formation and/or maturation of NCE invaginations...
May 12, 2017: Science
https://www.readbyqxmd.com/read/28495615/a-novel-function-of-tlr4-in-mediating-the-immunomodulatory-effect-of-benzanthrone-an-environmental-pollutant
#18
Prachi Tewari, Payal Mandal, Ruchi Roy, Somya Asthana, Premendra D Dwivedi, Mukul Das, Anurag Tripathi
Our prior studies have reported that Benzanthrone (BA) manifests inflammatory responses in the spleen of Balb/c mice. The present investigation was carried out to study the impact of BA on macrophages, which are the primary scavenger cells in the body that act as a connecting link between innate and adaptive immunity. Parenteral administration of BA (daily for one week) to mice resulted in enhanced levels of nitric oxide (NO) and overexpression of inflammatory markers (COX-2, MMP-9 and PGE-2) in macrophages; however the level of MHC class-I and MHC class-II receptors were down regulated...
July 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28481020/activation-of-ryanodine-receptors-is-required-for-pka-mediated-downregulation-of-a-type-k-channels-in-rat-hippocampal-neurons
#19
Yoon-Sil Yang, Sang-Chan Jeon, Moon-Suk Kang, Seon-Hee Kim, Su-Yong Eun, Soo-Hee Jin, Sung-Cherl Jung
A-type K(+) channels (IA channels) contribute to learning and memory mechanisms by regulating neuronal excitabilities in the CNS, and their expression level is targeted by Ca(2+) influx via synaptic NMDA receptors (NMDARs) during long-term potentiation (LTP). However, it is not clear how local synaptic Ca(2+) changes induce IA downregulation throughout the neuron, extending from the active synapse to the soma. In this study, we tested if two major receptors of endoplasmic reticulum (ER), ryanodine (RyRs), and IP3 (IP3 R) receptors, are involved in Ca(2+) -mediated IA downregulation in cultured hippocampal neurons of rats...
May 8, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28473752/spontaneous-ca-2-influx-in-drosophila-pupal-neurons-is-modulated-by-ip3-receptor-function-and-influences-maturation-of-the-flight-circuit
#20
Sumita Chakraborty, Gaiti Hasan
Inositol 1,4,5-trisphosphate receptors (IP3R) are Ca(2+) channels on the neuronal endoplasmic reticulum (ER) membrane. They are gated by IP3, produced upon external stimulation and activation of G protein-coupled receptors on the plasma membrane (PM). IP3-mediated Ca(2+) release, and the resulting depletion of the ER store, triggers entry of extracellular Ca(2+) by store-operated Ca(2+) entry (SOCE). Mutations in IP3R attenuate SOCE. Compromised IP3R function and SOCE during pupal development of Drosophila leads to flight deficits and mimics suppression of neuronal activity during pupal or adult development...
2017: Frontiers in Molecular Neuroscience
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