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https://www.readbyqxmd.com/read/28211945/ip3-receptor-mutations-and-brain-diseases-in-human-and-rodents
#1
REVIEW
Chihiro Hisatsune, Katsuhiko Mikoshiba
The inositol 1,4,5 trisphosphate receptor (IP3 R) is a huge Ca(2+) channel that is localized at the endoplasmic reticulum (ER). The IP3 R releases Ca(2+) from the ER upon binding to IP3 , which is produced by various extracellular stimuli through phospholipase C activation. All vertebrate organisms have three subtypes of IP3 R genes, which have distinct properties of IP3 -binding and Ca(2+) sensitivity, and are differently regulated by phosphorylation and by their associated proteins. Each cell type expresses the three subtypes of IP3 R in a distinct proportion, which is important for creating and maintaining spatially and temporally appropriate intracellular Ca(2+) level patterns for the regulation of specific physiological phenomena...
February 17, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28199326/a-mathematical-model-of-calcium-dynamics-in-hsy-cells
#2
Jung Min Han, Akihiko Tanimura, Vivien Kirk, James Sneyd
Saliva is an essential part of activities such as speaking, masticating and swallowing. Enzymes in salivary fluid protect teeth and gums from infectious diseases, and also initiate the digestion process. Intracellular calcium (Ca2+) plays a critical role in saliva secretion and regulation. Experimental measurements of Ca2+ and inositol trisphosphate (IP3) concentrations in HSY cells, a human salivary duct cell line, show that when the cells are stimulated with adenosine triphosphate (ATP) or carbachol (CCh), they exhibit coupled oscillations with Ca2+ spike peaks preceding IP3 spike peaks...
February 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28179071/the-bh4-domain-of-bcl-2-orthologues-from-different-classes-of-vertebrates-can-act-as-an-evolutionary-conserved-inhibitor-of-ip3-receptor-channels
#3
Hristina Ivanova, Tomas Luyten, Elke Decrock, Tim Vervliet, Luc Leybaert, Jan B Parys, Geert Bultynck
Ca(2+) signalling plays an important role in various physiological processes in vertebrates. In mammals, the highly conserved anti-apoptotic B-cell lymphoma-2 (Bcl-2) protein is an important modulator of the inositol 1,4,5-trisphosphate receptor (IP3R), i.e. the main intracellular Ca(2+) - release channel located at the endoplasmic reticulum (ER). The Bcl-2 Homology (BH) 4 domain of Bcl-2 (BH4-Bcl-2) is a critical determinant for inhibiting IP3Rs, by directly targeting a region in the modulatory domain of the receptor (domain 3)...
January 25, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28167901/astrocytic-ip3-ca-2-signaling-modulates-theta-rhythm-and-rem-sleep
#4
Jeannine Foley, Tamara Blutstein, SoYoung Lee, Christophe Erneux, Michael M Halassa, Philip Haydon
Rapid eye movement (REM) sleep onset is triggered by disinhibition of cholinergic neurons in the pons. During REM sleep, the brain exhibits prominent activity in the 5-8 Hz (theta) frequency range. How REM sleep onset and theta waves are regulated is poorly understood. Astrocytes, a non-neuronal cell type in the brain, respond to cholinergic signals by elevating their intracellular Ca(2+) concentration. The goal of this study was to assess the sleep architecture of mice with attenuated IP3 mediated Ca(2+) signaling in astrocytes...
2017: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/28151934/hepatitis-b-virus-modulates-store-operated-calcium-entry-to-enhance-viral-replication-in-primary-hepatocytes
#5
Jessica C Casciano, Nicholas J Duchemin, R Jason Lamontagne, Laura F Steel, Michael J Bouchard
Many viruses modulate calcium (Ca2+) signaling to create a cellular environment that is more permissive to viral replication, but for most viruses that regulate Ca2+ signaling, the mechanism underlying this regulation is not well understood. The hepatitis B virus (HBV) HBx protein modulates cytosolic Ca2+ levels to stimulate HBV replication in some liver cell lines. A chronic HBV infection is associated with life-threatening liver diseases, including hepatocellular carcinoma (HCC), and HBx modulation of cytosolic Ca2+ levels could have an important role in HBV pathogenesis...
2017: PloS One
https://www.readbyqxmd.com/read/28145731/coupling-of-airway-smooth-muscle-tas2rs-to-intracellular-signaling-and-relaxation-is-via-g%C3%AE-i1-2-3
#6
Donghwa Kim, Jung A Woo, Ezekiel Geffken, Steven S An, Stephen B Liggett
Bitter taste receptors (TAS2Rs) are expressed on human airway smooth muscle (HASM) and evoke marked relaxation. Agonist interaction with TAS2Rs activates PLC and increases compartmentalized [Ca(2+)]i via IP3. In taste cells, the G-protein gustducin couples TAS2R to PLC, however we find very low levels of Gαgust mRNA or protein in HASM. We hypothesized that another G-protein in HASM transmits TAS2R function. TAS2R signaling to [Ca(2+)]i, ERK1/2, and physiologic relaxation was sensitive to pertussis toxin confirming a role for a member of the Gi-family...
February 1, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28145469/high-throughput-screen-detects-calcium-signaling-dysfunction-in-typical-sporadic-autism-spectrum-disorder
#7
Galina Schmunk, Rachel L Nguyen, David L Ferguson, Kenny Kumar, Ian Parker, J Jay Gargus
Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental disorders without any defined uniting pathophysiology. Ca(2+) signaling is emerging as a potential node in the genetic architecture of the disorder. We previously reported decreased inositol trisphosphate (IP3)-mediated Ca(2+) release from the endoplasmic reticulum in several rare monogenic syndromes highly comorbid with autism - fragile X and tuberous sclerosis types 1 and 2 syndromes. We now extend those findings to a cohort of subjects with sporadic ASD without any known mutations...
February 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28137231/insp3-signaling-in-apicomplexan-parasites
#8
Celia R S Garcia, Eduardo Alves, Pedro H S Pereira, Paula J Bartlett, Andrew P Thomas, Katsuhiko Mikoshiba, Helmut Plattner, L David Sibley
Phosphoinositides (PIs) and their derivatives are essential cellular components that form the building blocks for cell membranes and regulate numerous cell functions. Specifically, the ability to generate myo-inositol 1,4,5-trisphosphate (InsP3) via phospholipase C (PLC) dependent hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) to InsP3 and diacylglycerol (DAG) initiates intracellular calcium signaling events representing a fundamental signaling mechanism dependent on PIs. InsP3 produced by PI turnover as a second messenger causes intracellular calcium release, especially from endoplasmic reticulum, by binding to the InsP3 receptor (InsP3R)...
January 30, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28132831/transient-opening-of-the-mitochondrial-permeability%C3%A2-transition-pore-induces-microdomain-calcium-transients-in-astrocyte-processes
#9
Amit Agarwal, Pei-Hsun Wu, Ethan G Hughes, Masahiro Fukaya, Max A Tischfield, Abraham J Langseth, Denis Wirtz, Dwight E Bergles
Astrocytes extend highly branched processes that form functionally isolated microdomains, facilitating local homeostasis by redistributing ions, removing neurotransmitters, and releasing factors to influence blood flow and neuronal activity. Microdomains exhibit spontaneous increases in calcium (Ca(2+)), but the mechanisms and functional significance of this localized signaling are unknown. By developing conditional, membrane-anchored GCaMP3 mice, we found that microdomain activity that occurs in the absence of inositol triphosphate (IP3)-dependent release from endoplasmic reticulum arises through Ca(2+) efflux from mitochondria during brief openings of the mitochondrial permeability transition pore...
February 8, 2017: Neuron
https://www.readbyqxmd.com/read/28130845/neuron-astrocyte-signaling-is-preserved-in-the-aging-brain
#10
Marta Gómez-Gonzalo, Mario Martin-Fernandez, Ricardo Martínez-Murillo, Sara Mederos, Alicia Hernández-Vivanco, Stephanie Jamison, Ana P Fernandez, Julia Serrano, Pilar Calero, Hunter S Futch, Rubén Corpas, Coral Sanfeliu, Gertrudis Perea, Alfonso Araque
Astrocytes play crucial roles in brain homeostasis and are emerging as regulatory elements of neuronal and synaptic physiology by responding to neurotransmitters with Ca(2+) elevations and releasing gliotransmitters that activate neuronal receptors. Aging involves neuronal and astrocytic alterations, being considered risk factor for neurodegenerative diseases. Most evidence of the astrocyte-neuron signaling is derived from studies with young animals; however, the features of astrocyte-neuron signaling in adult and aging brain remain largely unknown...
April 2017: Glia
https://www.readbyqxmd.com/read/28122499/uridine-stimulate-laxative-effect-in-the-loperamide-induced-constipation-of-sd-rats-through-regulation-of-the-machrs-signaling-pathway-and-mucin-secretion
#11
Ji Eun Kim, Jun Go, Ji Eun Sung, Hyun Ah Lee, Woo Bin Yun, Jin Tae Hong, Dae Youn Hwang
BACKGROUND: Uridine (Urd), which has been reported as a major component of RNA, plays an important role in various biological process including neuroprotection, biochemical modulation and glycolysis, although its role in constipation has yet to be established. Therefore, in this study, we investigated the laxative effects of Urd on chronic constipation. METHODS: The constipation phenotypes and their related mechanisms were investigated in the transverse colons of SD rats with loperamide (Lop)-induced constipation after treatment with 100 mg/kg of Urd...
January 26, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28118027/impaired-relaxation-of-airway-smooth-muscle-in-mice-lacking-the-actin-binding-protein-gelsolin
#12
Maya Mikami, Yi Zhang, Jennifer Danielsson, Tiarra Joell, Hwan Mee Yong, Elizabeth Townsend, Seema Khurana, Steven S An, Charles W Emala
Diverse classes of ligands have recently been discovered that relax airway smooth muscle (ASM) despite a transient increase in intracellular calcium concentrations ([Ca(2+)]i). However, the cellular mechanisms are not well understood. Gelsolin is a calcium-activated actin severing and capping protein found in many cell types including ASM cells. Gelsolin also binds to phosphatidylinositol 4,5-bisphosphate (PIP2) making this substrate less available for phospholipase Cβ-mediated hydrolysis to inositol triphosphate (IP3) and diacylglycerol...
January 24, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28115480/sexual-dimorphism-in-a-reciprocal-interaction-of-ryanodine-and-ip3-receptors-in-the-induction-of-hyperalgesic-priming
#13
Eugen V Khomula, Luiz F Ferrari, Dionéia Araldi, Jon D Levine
: Hyperalgesic priming, a model of pain chronification in the rat is mediated by ryanodine receptor-dependent calcium release. While ryanodine induces priming in both sexes, females are 5-orders of magnitude more sensitive, by an estrogen receptor alpha (EsRα)-dependent mechanism. An inositol 1,4,5-triphosphate (IP3) receptor inhibitor prevented the induction of priming by ryanodine. For IP3 induced priming, females were also more sensitive. IP3-induced priming was prevented by pre-treatment with inhibitors of the sarco-endoplasmic reticulum calcium ATPase and ryanodine receptor...
January 23, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28108028/comparison-of-ca-2-puffs-evoked-by-extracellular-agonists-and-photoreleased-ip3
#14
Jeffrey T Lock, Ian F Smith, Ian Parker
The inositol trisphosphate (IP3) signaling pathway evokes local Ca(2+) signals (Ca(2+) puffs) that arise from the concerted openings of clustered IP3 receptor/channels in the ER membrane. Physiological activation is triggered by binding of agonists to G-protein-coupled receptors (GPCRs) on the cell surface, leading to cleavage of phosphatidyl inositol bisphosphate and release of IP3 into the cytosol. Photorelease of IP3 from a caged precursor provides a convenient and widely employed means to study the final stage of IP3-mediated Ca(2+) liberation, bypassing upstream signaling events to enable more precise control of the timing and relative concentration of cytosolic IP3...
December 5, 2016: Cell Calcium
https://www.readbyqxmd.com/read/28106298/inhibition-of-inositol-1-4-5-trisphosphate-receptor-induce-breast-cancer-cell-death-through-deregulated-autophagy-and-cellular-bioenergetics
#15
Aru Singh, Megha Chagtoo, Swasti Tiwari, Nelson George, Bandana Chakravarti, Sajid Khan, Sripada Lakshmi, Madan M Godbole
Inositol 1,4,5-trisphosphate receptors (IP3 Rs) regulate autophagy in normal cells and are associated with metastasis in cancer cells. In breast cancer, however, the regulation and role of IP3 Rs is not clear. To study this we used MCF-7 breast cancer cell line and mouse model of breast cancer. Inhibiting IP3 R sub types resulted in compromised bioenergetics both in terms of glucose and mitochondrial metabolism. The siRNA mediated silencing of IP3 R or its blocking by its inhibitors Xestospongin C and 2-Amino-ethoxy diphenyl borate increased cell death and LC3II expression in MCF-7 cells as well as attenuated cellular bioenergetics...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28099849/cyclic-amp-recruits-a-discrete-intracellular-ca-2-store-by-unmasking-hypersensitive-ip3-receptors
#16
Vera Konieczny, Stephen C Tovey, Stefania Mataragka, David L Prole, Colin W Taylor
Inositol 1,4,5-trisphosphate (IP3) stimulates Ca(2+) release from the endoplasmic reticulum (ER), and the response is potentiated by 3',5'-cyclic AMP (cAMP). We investigated this interaction in HEK293 cells using carbachol and parathyroid hormone (PTH) to stimulate formation of IP3 and cAMP, respectively. PTH alone had no effect on the cytosolic Ca(2+) concentration, but it potentiated the Ca(2+) signals evoked by carbachol. Surprisingly, however, the intracellular Ca(2+) stores that respond to carbachol alone could be both emptied and refilled without affecting the subsequent response to PTH...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28094886/the-parathyroid-hormone-family-member-tip39-interacts-with-sarco-endoplasmic-reticulum-ca-2-atpase-activity-by-influencing-calcium-homeostasis
#17
Emi Sato, Michael R Williams, James A Sanford, George L Sen, Takekuni Nakama, Shinichi Imafuku, Richard L Gallo
Darier disease (DD) is a genetic skin disease that is associated with mutations in the ATP2A2 gene encoding the type 2 sarco/endoplasmic reticulum Ca(2+) -ATPase (SERCA2). Mutations of this gene result in alterations of calcium homeostasis, abnormal epidermal adhesion and dyskeratosis. Silencing of ATP2A2 in monolayer cell culture of keratinocytes reduces desmoplakin expression at the borders of cells and impacts cell adhesion. Here, we report establishment of a three-dimensional (3D) epidermal model of DD, and use this model to evaluate peptide therapy with tuberoinfundibular peptide of 39 residues (TIP39) to normalize calcium transport...
January 17, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28066549/synthesis-of-dimeric-analogs-of-adenophostin-a-that-potently-evoke-ca-2-release-through-ip3-receptors
#18
Amol M Vibhute, Poornenth Pushpanandan, Maria Varghese, Vera Koniecnzy, Colin W Taylor, Kana M Sureshan
Inositol 1,4,5-trisphosphate receptors (IP3Rs) are tetrameric intracellular channels through which many extracellular stimuli initiate the Ca(2+) signals that regulate diverse cellular responses. There is considerable interest in developing novel ligands of IP3R. Adenophostin A (AdA) is a potent agonist of IP3R and since some dimeric analogs of IP3R ligands are more potent than the corresponding monomer; we considered whether dimeric AdA analogs might provide agonists with increased potency. We previously synthesized traizolophostin, in which a simple triazole replaced the adenine of AdA, and showed it to be equipotent to AdA...
November 3, 2016: RSC Advances
https://www.readbyqxmd.com/read/28063222/astrocytic-ip3-rs-contribution-to-ca-2-signalling-and-hippocampal-ltp
#19
Mark William Sherwood, Misa Arizono, Chihiro Hisatsune, Hiroko Bannai, Etsuko Ebisui, John Lawrence Sherwood, Aude Panatier, Stéphane Henri Richard Oliet, Katsuhiko Mikoshiba
Astrocytes regulate hippocampal synaptic plasticity by the Ca(2+) dependent release of the N-methyl d-aspartate receptor (NMDAR) co-agonist d-serine. Previous evidence indicated that d-serine release would be regulated by the intracellular Ca(2+) release channel IP3 receptor (IP3 R), however, genetic deletion of IP3 R2, the putative astrocytic IP3 R subtype, had no impact on synaptic plasticity or transmission. Although IP3 R2 is widely believed to be the only functional IP3 R in astrocytes, three IP3 R subtypes (1, 2, and 3) have been identified in vertebrates...
January 7, 2017: Glia
https://www.readbyqxmd.com/read/28051147/%C3%AE-2-adrenoreceptor-inverse-agonist-down-regulates-muscarine-cholinergic-subtype-3-receptor-and-its-downstream-signal-pathways-in-airway-smooth-muscle-cells-in-vitro
#20
Jian Luo, Yuan-Hua Liu, Wei Luo, Zhu Luo, Chun-Tao Liu
Mechanisms underlying β2-adrenoreceptor (β2AR) inverse agonist mediated bronchoprotectiveness remain unknown. We incubated ICI118,551, formoterol, budesonide, and formoterol plus budesonide, as well as ICI118,551 or pindolol plus formoterol, ICI118,551 plus forskolin, SQ22,536 or H89 plus formoterol in ASMCs to detect expressions of M3R, PLCβ1 and IP3. The level of M3R in the presence of 10(-5) mmol/L ICI118,551 were significantly decreased at 12 h, 24 h and 48 h (P < 0.05), and at 24 h were significantly reduced in ICI118,551 with concentration of 10(-5 )mmol/L, 10(-6 )mmol/L, 10(-7 )mmol/L, and 10(-8 )mmol/L (P < 0...
January 4, 2017: Scientific Reports
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