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https://www.readbyqxmd.com/read/28066549/synthesis-of-dimeric-analogs-of-adenophostin-a-that-potently-evoke-ca-2-release-through-ip3-receptors
#1
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
#2
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
#3
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
https://www.readbyqxmd.com/read/28031098/mechanical-strain-regulates-osteoblast-proliferation-through-ca-2-camk-creb-signal-pathway
#4
Yong Guo, Qi Lv, Xian-Qiong Zou, Zhi-Xiong Yan, Yu-Xian Yan
Objective To investigate the effects of mechanical strain on Ca(2+)-calmodulin dependent kinase (CaMK)-cAMP response element binding protein (CREB) signal pathway and proliferation of osteoblasts.Methods Using a four-point bending device, MC3T3-E1 cells were exposed to mechanical tensile strains of 2500 µs and 5000 µs at 0.5 Hz respectively. The intracellular free Ca(2+) ([Ca(2+)]i) concentration and calmodulin activity were assayed by fluorospectrophotometry, CaMK II β, CREB, and phosphorylated (activated) CREB (p-CREB) were assessed by Western blot, and cells proliferation was assayed with MTT...
June 20, 2016: Chinese Medical Sciences Journal, Chung-kuo i Hsüeh K'o Hsüeh Tsa Chih
https://www.readbyqxmd.com/read/28013338/colon-cancer-cell-derived-12-s-hete-induces-the-retraction-of-cancer-associated-fibroblast-via-mlc2-rho-rock-and-ca-2-signalling
#5
Serena Stadler, Chi Huu Nguyen, Helga Schachner, Daniela Milovanovic, Silvio Holzner, Stefan Brenner, Julia Eichsteininger, Mira Stadler, Daniel Senfter, Liselotte Krenn, Wolfgang M Schmidt, Nicole Huttary, Sigurd Krieger, Oskar Koperek, Zsuzsanna Bago-Horvath, Konstantin Alexander Brendel, Brigitte Marian, Oliver de Wever, Robert M Mader, Benedikt Giessrigl, Walter Jäger, Helmut Dolznig, Georg Krupitza
Retraction of mesenchymal stromal cells supports the invasion of colorectal cancer cells (CRC) into the adjacent compartment. CRC-secreted 12(S)-HETE enhances the retraction of cancer-associated fibroblasts (CAFs) and therefore, 12(S)-HETE may enforce invasivity of CRC. Understanding the mechanisms of metastatic CRC is crucial for successful intervention. Therefore, we studied pro-invasive contributions of stromal cells in physiologically relevant three-dimensional in vitro assays consisting of CRC spheroids, CAFs, extracellular matrix and endothelial cells, as well as in reductionist models...
December 24, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28013061/voltage-and-receptor-mediated-activation-of-a-non-selective-cation-channel-in-rat-carotid-body-glomus-cells
#6
Jiaju Wang, James O Hogan, Donghee Kim
A recent study showed that hypoxia activates a Ca(2+)-sensitive, Na(+)-permeable non-selective cation channel (NSC) in carotid body glomus cells. We studied the effects of mitochondrial inhibitors that increase Ca(2+) influx via Ca(2+) channel (Cav), and receptor agonists that release Ca(2+) from endoplasmic reticulum (ER) on NSC. Mitochondrial inhibitors (NaCN, FCCP, H2S, NO) elevated [Ca(2+)]i and activated NSC. Angiotensin II and acetylcholine that elevate [Ca(2+)]i via the Gq-IP3 pathway activated NSC. However, endothelin-1 (Gq) and 5-HT (Gq) showed little or no effect on [Ca(2+)]i and did not activate NSC...
December 21, 2016: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28011630/a-polycycstin-type-transient-receptor-potential-trp-channel-that-is-activated-by-atp
#7
David Traynor, Robert R Kay
ATP and ADP are ancient extra-cellular signalling molecules that in Dictyostelium amoebae cause rapid, transient increases in cytosolic calcium due to an influx through the plasma membrane. This response is independent of hetero-trimeric G-proteins, the putative IP3 receptor IplA and all P2X channels. We show, unexpectedly, that it is abolished in mutants of the polycystin-type transient receptor potential channel, TrpP. Responses to the chemoattractants cyclic-AMP and folic acid are unaffected in TrpP mutants...
December 23, 2016: Biology Open
https://www.readbyqxmd.com/read/28007573/5-6-%C3%AE-dhtl-a-stable-metabolite-of-arachidonic-acid-is-a-potential-edhf-that-mediates-microvascular-dilation
#8
Reut Levi-Rosenzvig, Andreas M Beyer, Joseph Hockenberry, Rotem Shelly Ben-Shushan, Dimitry Chuyun, Shahar Atiya, Snait Tamir, David D Gutterman, Andrea Szuchman-Sapir
OBJECTIVE: Prominent among the endothelium-derived hyperpolarizing factors (EDHFs) are the Cytochrome P450 (CYP) epoxygenase-derived arachidonic acid metabolites-the epoxyeicosatrienoic acids (EETs), that are known as vasodilators in the microcirculation. Among the EET isomers, 5,6-EET undergoes rapid lactonization in aqueous solution to the more stable 5,6-δ DHTL (5,6-dihydroxytrienoic lactone) isomer. It is unclear whether this metabolic transformation maintains its vasodilator potential and what is the mechanism of action...
December 19, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27995898/irbit-controls-apoptosis-by-interacting-with-the-bcl-2-homolog-bcl2l10-and-by-promoting-er-mitochondria-contact
#9
Benjamin Bonneau, Hideaki Ando, Katsuhiro Kawaai, Matsumi Hirose, Hiromi Takahashi-Iwanaga, Katsuhiko Mikoshiba
IRBIT is a molecule that interacts with the inositol 1,4,5-trisphosphate (IP3)-binding pocket of the IP3 receptor (IP3R), whereas the antiapoptotic protein, Bcl2l10, binds to another part of the IP3-binding domain. Here we show that Bcl2l10 and IRBIT interact and exert an additive inhibition of IP3R in the physiological state. Moreover, we found that these proteins associate in a complex in mitochondria-associated membranes (MAMs) and that their interplay is involved in apoptosis regulation. MAMs are a hotspot for Ca(2+) transfer between endoplasmic reticulum (ER) and mitochondria, and massive Ca(2+) release through IP3R in mitochondria induces cell death...
December 20, 2016: ELife
https://www.readbyqxmd.com/read/27941214/calcium-alterations-signal-either-to-senescence-or-to-autophagy-induction-in-stem-cells-upon-oxidative-stress
#10
Aleksandra V Borodkina, Alla N Shatrova, Pavel I Deryabin, Anastasiia A Griukova, Polina A Abushik, Sergei M Antonov, Nikolay N Nikolsky, Elena B Burova
Intracellular calcium ([Ca(2+)]i) has been reported to play an important role in autophagy, apoptosis and necrosis, however, a little is known about its impact in senescence. Here we investigated [Ca(2+)]i contribution to oxidative stress-induced senescence of human endometrium-derived stem cells (hMESCs). In hMESCs sublethal H2O2-treatment resulted in a rapid calcium release from intracellular stores mediated by the activation of PLC/IP3/IP3R pathway. Notably, further senescence development was accompanied by persistently elevated [Ca(2+)]i levels...
December 8, 2016: Aging
https://www.readbyqxmd.com/read/27941021/plc%C3%AE-1-controls-osteoclast-numbers-via-csf-1-dependent-diacylglycerol-%C3%AE-catenin-cyclind1-pathway
#11
Zhengfeng Yang, Seokho Kim, Sahil Mahajan, Ali Zamani, Roberta Faccio
Phospholipase C gamma (PLCγ) 1 and 2 are a class of highly homologous enzymes modulating a variety of cellular pathways through production of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). Our previous studies demonstrated the importance of PLCγ2 in osteoclast (OC) differentiation by modulating IP3-mediated calcium oscillations and the upregulation of the transcription factor NFATc1. Surprisingly, despite being expressed throughout osteoclastogenesis, PLCγ1 did not compensate for PLCγ2 deficiency...
December 9, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27939335/calcium-signalling-induced-by-in-vitro-exposure-to-silicium-dioxide-nanoparticles-in-rat-pulmonary-artery-smooth-muscle-cells
#12
Virginie Dubes, Thibaud Parpaite, Thomas Ducret, Jean-François Quignard, Stéphane Mornet, Nora Reinhardt, Isabelle Baudrimont, Mathilde Dubois, Véronique Freund-Michel, Roger Marthan, Bernard Muller, Jean-Pierre Savineau, Arnaud Courtois
The development and use of nanomaterials, especially engineered nanoparticles (NP), is expected to provide many benefits. But at the same time the development of such materials is also feared because of their potential human health risks. Indeed, NP display some characteristics similar to ultrafine environmental particles which are known to exert deleterious cardiovascular effects including pro-hypertensive ones. In this context, the effect of NP on calcium signalling, whose deregulation is often involved in hypertensive diseases, remain poorly described...
January 15, 2017: Toxicology
https://www.readbyqxmd.com/read/27935256/pigment-translocation-in-caridean-shrimp-chromatophores-receptor-type-signal-transduction-second-messengers-and-cross-talk-among-multiple-signaling-cascades
#13
Sarah Ribeiro Milograna, Márcia Regina Ribeiro, Fernanda Tinti Bell, John Campbell McNAMARA
Pigment aggregation in shrimp chromatophores is triggered by red pigment concentrating hormone (RPCH), a neurosecretory peptide whose plasma membrane receptor may be a G-protein coupled receptor (GPCR). While RPCH binding activates the Ca(2+) /cGMP signaling cascades, a role for cyclic AMP (cAMP) in pigment aggregation is obscure, as are the steps governing Ca(2+) release from the smooth endoplasmic reticulum (SER). A role for the antagonistic neuropeptide, pigment dispersing homone (α-PDH) is also unclear...
December 9, 2016: Journal of Experimental Zoology. Part A, Ecological Genetics and Physiology
https://www.readbyqxmd.com/read/27923677/intact-mitochondrial-ca-2-uniport-is-essential-for-agonist-induced-activation-of-endothelial-nitric-oxide-synthase-enos
#14
Suphachai Charoensin, Emrah Eroglu, Marissa Opelt, Helmut Bischof, Corina T Madreiter-Sokolowski, Andrijana Kirsch, Maria R Depaoli, Saša Frank, Astrid Schrammel, Bernd Mayer, Markus Waldeck-Weiermair, Wolfgang F Graier, Roland Malli
Mitochondrial Ca(2+) uptake regulates diverse endothelial cell functions and has also been related to nitric oxide (NO(•)) production. However, it is not entirely clear if the organelles support or counteract NO(•) biosynthesis by taking up Ca(2+). The objective of this study was to verify whether or not mitochondrial Ca(2+) uptake influences Ca(2+)-triggered NO(•) generation by endothelial NO(•) synthase (eNOS) in an immortalized endothelial cell line (EA.hy926), respective primary human umbilical vein endothelial cells (HUVECs) and eNOS-RFP (red fluorescent protein) expressing human embryonic kidney (HEK293) cells...
January 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27922695/effects-of-five-candidate-laxatives-derived-from-liriope-platyphylla-on-the-5-ht-receptor-signaling-pathway-in-three-cell-types-present-in-the-transverse-colon
#15
Ji Eun Kim, Eun Kyoung Koh, Sung Hwa Song, Ji Eun Sung, Hyun Ah Lee, Hong Gu Lee, Young Whan Choi, Dae Youn Hwang
The laxative effects of aqueous extract of Liriope platyphylla (AEtLP) on loperamide (Lop)‑induced constipation have been reported; however, the key compounds and the mechanism underlying these effects remain unclear. Therefore, the laxative effects of five candidates derived from L. platyphylla: Diosgenin (DG), 5-hydroxymethylfurfural (5-HMF), adenosine (AD), hydroxypropyl cellulose (HPC) and uridine (UD) were investigated by examining the alteration of G protein α (Gα) expression, protein kinase C (PKC) phosphorylation and inositol triphosphate (IP3) concentration levels in the 5-hydroxytryptamine (5‑HT; serotonin) receptor signaling pathway...
January 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27922641/ip3-accumulation-and-or-inositol-depletion-two-downstream-lithium-s-effects-that-may-mediate-its-behavioral-and-cellular-changes
#16
Y Sade, L Toker, N Z Kara, H Einat, S Rapoport, D Moechars, G T Berry, Y Bersudsky, G Agam
Lithium is the prototype mood stabilizer but its mechanism is still unresolved. Two hypotheses dominate-the consequences of lithium's inhibition of inositol monophosphatase at therapeutically relevant concentrations (the 'inositol depletion' hypothesis), and of glycogen-synthase kinase-3. To further elaborate the inositol depletion hypothesis that did not decisively determine whether inositol depletion per se, or phosphoinositols accumulation induces the beneficial effects, we utilized knockout mice of either of two inositol metabolism-related genes-IMPA1 or SMIT1, both mimic several lithium's behavioral and biochemical effects...
December 6, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27919026/hindered-cytoplasmic-diffusion-of-inositol-trisphosphate-restricts-its-cellular-range-of-action
#17
George D Dickinson, Kyle L Ellefsen, Silvina Ponce Dawson, John E Pearson, Ian Parker
The range of action of intracellular messengers is determined by their rates of diffusion and degradation. Previous measurements in oocyte cytoplasmic extracts indicated that the Ca(2+)-liberating second messenger inositol trisphosphate (IP3) diffuses with a coefficient (~280 μm(2) s(-1)) similar to that in water, corresponding to a range of action of ~25 μm. Consequently, IP3 is generally considered a "global" cellular messenger. We reexamined this issue by measuring local IP3-evoked Ca(2+) puffs to monitor IP3 diffusing from spot photorelease in neuroblastoma cells...
November 8, 2016: Science Signaling
https://www.readbyqxmd.com/read/27919025/ip3-still-on-the-move-but-now-in-the-slow-lane
#18
REVIEW
Luc Leybaert
In this issue of Science Signaling, Dickinson et al show that the intracellular messenger inositol 1,4,5-trisphosphate (IP3), which triggers the release of calcium (Ca(2+)) from the endoplasmic reticulum, is a slowly diffusing local signal, rather than a rapidly diffusing global one. These findings have implications for the understanding of the mechanisms of Ca(2+) wave propagation, especially long-range, cell-to-cell propagating Ca(2+) waves.
November 8, 2016: Science Signaling
https://www.readbyqxmd.com/read/27904901/effect-of-ticagrelor-on-endothelial-calcium-signalling-and-barrier-function
#19
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
#20
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
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