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https://www.readbyqxmd.com/read/27904901/effect-of-ticagrelor-on-endothelial-calcium-signalling-and-barrier-function
#1
Dursun Gündüz, Christian Tanislav, Klaus-Dieter Schlüter, Rainer Schulz, Christian Hamm, Muhammad Aslam
The P2Y12 receptor is a Gi-coupled receptor whose activation inhibits adenylyl cyclase and thereby reduces the concentration of intracellular cAMP. Here the hypothesis was tested whether AR-C 66096 or ticagrelor, two direct-acting and reversibly binding P2Y12 receptor antagonists, protect endothelial cell (EC) barrier function by raising intracellular cAMP in ECs. The study was carried out on primary human umbilical vein ECs (HUVECs) and human pulmonary microvascular ECs (hPMECs). AR-C66096 (10 µM) induced a 50 % increase in cAMP in ECs whereas ticagrelor (2-10 µM) had no effect...
December 1, 2016: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/27888240/topological-organisation-of-the-phosphatidylinositol-4-5-bisphosphate-phospholipase-c-resynthesis-cycle-pitps-bridge-the-er-pm-gap
#2
REVIEW
Shamshad Cockcroft, Padinjat Raghu
Phospholipase C (PLC) is a receptor-regulated enzyme that hydrolyses phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) at the plasma membrane (PM) triggering three biochemical consequences, the generation of soluble inositol 1,4,5-trisphosphate (IP3), membrane-associated diacylglycerol (DG) and the consumption of PM PI(4,5)P2 Each of these three signals triggers multiple molecular processes impacting key cellular properties. The activation of PLC also triggers a sequence of biochemical reactions, collectively referred to as the PI(4,5)P2 cycle that culminates in the resynthesis of this lipid...
December 1, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27887748/probes-for-manipulating-and-monitoring-ip3
#3
REVIEW
Akitoshi Miyamoto, Katsuhiko Mikoshiba
Inositol 1,4,5-trisphosphate (IP3) is an important second messenger produced via G-protein-coupled receptor- or receptor tyrosine kinase-mediated pathways. IP3 levels induce Ca(2+) release from the endoplasmic reticulum (ER) via IP3 receptor (IP3R) located in the ER membrane. The resultant spatiotemporal pattern of Ca(2+) signals regulates diverse cellular functions, including fertilization, gene expression, synaptic plasticity, and cell death. Therefore, monitoring and manipulating IP3 levels is important to elucidate not only the functions of IP3-mediated pathways but also the encoding mechanism of IP3R as a converter of intracellular signals from IP3 to Ca(2+)...
November 17, 2016: Cell Calcium
https://www.readbyqxmd.com/read/27881333/-role-of-pannexin-1-channels-in-cisplatin-induced-apoptosis-in-i-10-cells
#4
Jian-Feng Wu, Shu-Ying Dong, Dan-Dan Wu, Yin-Ling Chen, Xu-Hui Tong
OBJECTIVE: To investigate the role of pannexin 1 channels in cisplatin-induced apoptosis in I-10 cells and the mechanisms. METHODS: MTT assay was used to assess the cytotoxicity of cisplatin (DDP) in I-10 cells. Annexin V/PI double staining and Hoechst 33258 fluorescence staining were employed to detect early- and late-stage apoptosis of the cells, respectively. Extracellular ATP level and intracellular IP3 level in the cells were detected using commercial detection kits...
November 20, 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/27856517/mglur-long-term-depression-regulates-glua2-association-with-copii-vesicles-and-exit-from-the-endoplasmic-reticulum
#5
Joseph E Pick, Latika Khatri, Matheus F Sathler, Edward B Ziff
mGluR long-term depression (mGluR-LTD) is a form of synaptic plasticity induced at excitatory synapses by metabotropic glutamate receptors (mGluRs). mGluR-LTD reduces synaptic strength and is relevant to learning and memory, autism, and sensitization to cocaine; however, the mechanism is not known. Here we show that activation of Group I mGluRs in medium spiny neurons induces trafficking of GluA2 from the endoplasmic reticulum (ER) to the synapse by enhancing GluA2 binding to essential COPII vesicle proteins, Sec23 and Sec13...
November 17, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27848113/calcium-waves-in-a-grid-of-clustered-channels-with-synchronous-ip3-binding-and-unbinding
#6
M Rückl, S Rüdiger
Calcium signals in cells occur at multiple spatial scales and variable temporal duration. However, a physical explanation for transitions between long-lasting global oscillations and localized short-term elevations (puffs) of cytoplasmic Ca(2+) is still lacking. Here we introduce a phenomenological, coarse-grained model for the calcium variable, which is represented by ordinary differential equations. Due to its small number of parameters, and its simplicity, this model allows us to numerically study the interplay of multi-scale calcium concentrations with stochastic ion channel gating dynamics even in larger systems...
November 2016: European Physical Journal. E, Soft Matter
https://www.readbyqxmd.com/read/27836216/regulation-of-ip3-receptors-by-cyclic-amp
#7
REVIEW
Colin W Taylor
Ca(2+) and cAMP are ubiquitous intracellular messengers and interactions between them are commonplace. Here the effects of cAMP on inositol 1,4,5-trisphosphate receptors (IP3Rs) are briefly reviewed. All three subtypes of IP3R are phosphorylated by cAMP-dependent protein kinase (PKA). This potentiates IP3-evoked Ca(2+) release through IP3R1 and IP3R2, but probably has little effect on IP3R3. In addition, cAMP can directly sensitize all three IP3R subtypes to IP3. The high concentrations of cAMP required for this PKA-independent modulation of IP3Rs is delivered to them within signalling junctions that include type 6 adenylyl cyclase and IP3R2...
November 6, 2016: Cell Calcium
https://www.readbyqxmd.com/read/27830834/suilysin-induced-platelet-neutrophil-complexes-formation-is-triggered-by-pore-formation-dependent-calcium-influx
#8
Shengwei Zhang, Yuling Zheng, Shaolong Chen, Shujing Huang, Keke Liu, Qingyu Lv, Yongqiang Jiang, Yuan Yuan
Platelet activation and platelet-neutrophil interactions have been found to be involved in inflammation, organ failure and soft-tissue necrosis in bacterial infections. Streptococcus suis, an emerging human pathogen, can cause streptococcal toxic-shock syndrome (STSS) similarly to Streptococcus pyogenes. Currently, S. suis-platelet interactions are poorly understood. Here, we found that suilysin (SLY), the S. suis cholesterol-dependent cytolysin (CDC), was the sole stimulus of S. suis that induced platelet-neutrophil complexes (PNC) formation...
November 10, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27823962/the-transient-receptor-potential-ankyrin-1-mediates-mechanical-hyperalgesia-induced-by-the-activation-of-b1-receptor-in-mice
#9
Flavia Carla Meotti, Cláudia Pinto Figueiredo, Marianne Manjavachi, João B Calixto
The kinin receptor B1 and the transient receptor potential ankyrin 1 (TRPA1) work as initiators and gatekeepers of nociception and inflammation. This study reports that the nociceptive transmission induced by activation of B1 receptor is dependent on TRPA1 ion channel. The mechanical hyperalgesia was induced by intrathecal (i.t.) injection of B1 agonist des-Arginine(9)-bradykinin (DABK) or TRPA1 agonist cinnamaldehyde and was evaluated by the withdrawal response after von Frey Hair application in the hind paw...
November 4, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27807138/critical-role-of-atp-induced-atp-release-for-ca2-signaling-in-nonsensory-cell-networks-of-the-developing-cochlea
#10
Federico Ceriani, Tullio Pozzan, Fabio Mammano
Spatially and temporally coordinated variations of the cytosolic free calcium concentration ([Ca(2+)]c) play a crucial role in a variety of tissues. In the developing sensory epithelium of the mammalian cochlea, elevation of extracellular adenosine trisphosphate concentration ([ATP]e) triggers [Ca(2+)]c oscillations and propagation of intercellular inositol 1,4,5-trisphosphate (IP3)-dependent Ca(2+) waves. What remains uncertain is the relative contribution of gap junction channels and connexin hemichannels to these fundamental mechanisms, defects in which impair hearing acquisition...
November 2, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27800304/effects-of-suilysin-on-streptococcus-suis-induced-platelet-aggregation
#11
Shengwei Zhang, Junping Wang, Shaolong Chen, Jiye Yin, Zhiyuan Pan, Keke Liu, Lin Li, Yuling Zheng, Yuan Yuan, Yongqiang Jiang
Blood platelets play important roles during pathological thrombocytopenia in streptococcal toxic shock syndrome (STSS). Streptococcus suis (S. suis) an emerging human pathogen, can cause STSS similarly to S. pyogenes. However, S. suis interactions with platelets are poorly understood. Here, we found that suilysin (SLY), different from other bacterial cholesterol-dependent cytolysins (CDCs), was the sole stimulus that induced platelet aggregation. Furthermore, the inside-out activation of GPIIb/IIIa of platelets mediated SLY-induced platelet aggregation...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27788256/p2y1-receptor-signaling-contributes-to-high-salt-induced-priming-of-the-nlrp3-inflammasome-in-retinal-pigment-epithelial-cells
#12
Philipp Prager, Margrit Hollborn, Anja Steffen, Peter Wiedemann, Leon Kohen, Andreas Bringmann
BACKGROUND: Systemic hypertension is a risk factor of age-related macular degeneration (AMD), a chronic inflammatory disease. Acute hypertension is caused by increased extracellular osmolarity after intake of dietary salt (NaCl). We determined in cultured human retinal pigment epithelial (RPE) cells whether high extracellular NaCl alters the gene expression of inflammasome-associated proteins, and whether autocrine/paracrine purinergic (P2) receptor signaling contributes to the NaCl-induced NLRP3 gene expression...
2016: PloS One
https://www.readbyqxmd.com/read/27777977/ip3-receptors-regulate-vascular-smooth-muscle-contractility-and-hypertension
#13
Qingsong Lin, Guiling Zhao, Xi Fang, Xiaohong Peng, Huayuan Tang, Hong Wang, Ran Jing, Jie Liu, W Jonathan Lederer, Ju Chen, Kunfu Ouyang
Inositol 1, 4, 5-trisphosphate receptor-mediated (IP3R-mediated) calcium (Ca(2+)) release has been proposed to play an important role in regulating vascular smooth muscle cell (VSMC) contraction for decades. However, whether and how IP3R regulates blood pressure in vivo remains unclear. To address these questions, we have generated a smooth muscle-specific IP3R triple-knockout (smTKO) mouse model using a tamoxifen-inducible system. In this study, the role of IP3R-mediated Ca(2+) release in adult VSMCs on aortic vascular contractility and blood pressure was assessed following tamoxifen induction...
October 20, 2016: JCI Insight
https://www.readbyqxmd.com/read/27768902/regulation-of-proteasome-activity-by-p2y2-receptor-underlies-the-neuroprotective-effects-of-extracellular-nucleotides
#14
Laura de Diego-García, Mercedes Ramírez-Escudero, Álvaro Sebastián-Serrano, Juan Ignacio Diaz-Hernández, Jesús Pintor, José J Lucas, Miguel Díaz-Hernández
The Ubiquitin-Proteasome System (UPS) is essential for the regulation of the cellular proteostasis. Indeed, it has been postulated that an UPS dysregulation is the common mechanism that underlies several neurological disorders. Considering that extracellular nucleotides, through their selective P2Y2 receptor (P2Y2R), play a neuroprotective role in various neurological disorders that course with an UPS impairment, we wonder if this neuroprotective capacity resulted from their ability to modulate the UPS. Using a cellular model expressing two different UPS reporters, we found that the stimulation of P2Y2R by its selective agonist Up4U induced a significant reduction of UPS reporter levels...
October 18, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27768311/ip3-mediates-nitric-oxide-guanosine-3-5-cyclic-monophosphate-no-cgmp-induced-isoflavone-accumulation-in-soybean-sprouts-under-uv-b-radiation
#15
Caifeng Jiao, Pei Wang, Runqiang Yang, Lu Tian, Zhenxin Gu
In this study, to investigate the role of inositol 1,4,5-trisphosphate (IP3) in nitric oxide-guanosine 3',5'-cyclic monophosphate (NO-cGMP)-induced isoflavone accumulation in soybean sprouts under UV-B radiation, the sprouts were treated with donors and inhibitors of NO and cGMP as well as IP3 inhibitor. Results showed that NO, with cGMP as a second messenger, stimulates IP3 accumulation under UV-B radiation. Consistent with the increase in IP3 content, the up-regulation of gene and protein expression of phosphoinositide-specific phospholipase C (PI-PLC) in response to sodium nitroprusside (SNP) (exogenous NO donor) and 8-Br-cGMP (cGMP analogue) was also observed...
October 28, 2016: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/27761313/comparative-functional-characterization-of-novel-non-syndromic-gjb2-gene-variant-p-gly45arg-and-lethal-syndromic-variant-p-gly45glu
#16
Juan Rodriguez-Paris, Jörg Waldhaus, Jeenal A Gordhandas, Lynn Pique, Iris Schrijver
We characterized a novel GJB2 missense variant, c.133G>A, p.Gly45Arg, and compared it with the only other variant at the same amino acid position of the connexin 26 protein (Cx26) reported to date: c.134G>A, p.Gly45Glu. Whereas both variants are associated with hearing loss and are dominantly inherited, p.Gly45Glu has been implicated in the rare fatal keratitis-ichthyosis-deafness (KID) syndrome, which results in cutaneous infections and septicemia with premature demise in the first year of life. In contrast, p...
2016: PeerJ
https://www.readbyqxmd.com/read/27749281/comparison-of-gating-dynamics-of-different-ip3r-channels-with-immune-algorithm-searching-for-channel-parameter-distributions
#17
Xiuhong Cai, Xiang Li, Hong Qi, Fang Wei, Jianyong Chen, Jianwei Shuai
The gating properties of the inositol 1, 4, 5-trisphosphate (IP3) receptor (IP3R) are determined by the binding and unbinding capability of Ca(2+) ions and IP3 messengers. With the patch clamp experiments, the stationary properties have been discussed for Xenopus oocyte type-1 IP3R (Oo-IP3R1), type-3 IP3R (Oo-IP3R3) and Spodoptera frugiperda IP3R (Sf-IP3R). In this paper, in order to provide insights about the relation between the observed gating characteristics and the gating parameters in different IP3Rs, we apply the immune algorithm to fit the parameters of a modified DeYoung-Keizer model...
October 17, 2016: Physical Biology
https://www.readbyqxmd.com/read/27744004/histamine-h3-receptor-activation-stimulates-calcium-mobilization-in-a-subpopulation-of-rat-striatal-neurons-in-primary-culture-but-not-in-synaptosomes
#18
Nayeli Rivera-Ramírez, Wilber Montejo-López, María-Cristina López-Méndez, Agustín Guerrero-Hernández, Anayansi Molina-Hernández, Ubaldo García-Hernández, José-Antonio Arias-Montaño
The histamine H3 receptor (H3R) is abundantly expressed in the Central Nervous System where it regulates several functions pre and postsynaptically. H3Rs couple to Gαi/o proteins and trigger or modulate several intracellular signaling pathways, including the cAMP/PKA pathway and the opening of N- and P/Q-type voltage-gated Ca(2+) channels. In transfected cells, activation of the human H3R of 445 amino acids (hH3R445) results in phospholipase C (PLC) stimulation and release of Ca(2+) from intracellular stores...
December 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27743014/membrane-protein-quantity-control-at-the-endoplasmic-reticulum
#19
Ignat Printsev, Daniel Curiel, Kermit L Carraway
The canonical function of the endoplasmic reticulum-associated degradation (ERAD) system is to enforce quality control among membrane-associated proteins by targeting misfolded secreted, intra-organellar, and intramembrane proteins for degradation. However, increasing evidence suggests that ERAD additionally functions in maintaining appropriate levels of a subset of membrane-associated proteins. In this 'quantity control' capacity, ERAD responds to environmental cues to regulate the proteasomal degradation of specific ERAD substrates according to cellular need...
October 14, 2016: Journal of Membrane Biology
https://www.readbyqxmd.com/read/27732877/immunomodulatory-effect-of-aps-and-psp-is-mediated-by-ca2-camp-and-tlr4-nf-%C3%AE%C2%BAb-signaling-pathway-in-macrophage
#20
Zhixue Wang, Zijing Liu, Lijng Zhou, Tingting Long, Xing Zhou, Yixi Bao
OBJECTIVE: This study is to investigate the role of second messengers and TLR4/NF-κB signaling pathway in the immunomodulatory activities of Astragalus polysaccharide (APS) and Polysaccharopeptide (PSP) in macrophages. METHODS: RAW 264.7 macrophage cells were treated with APS, PSP, lipopolysaccharide (LPS), or NiCl2. Power-spectral method was used to detect protein kinase C (PKC) and Griess reaction to detect nitric oxide (NO). ELISA was conducted to detect cyclic adenosine monophosphate (cAMP), diglycerides (DAG), inositol 1, 4, 5-triphosphate (IP3), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)...
October 11, 2016: International Journal of Biological Macromolecules
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