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https://www.readbyqxmd.com/read/28549333/endoplasmic-reticulum-er-stress-and-camp-pka-pathway-mediated-zn-induced-hepatic-lipolysis
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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...
May 8, 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
#9
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
#10
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
https://www.readbyqxmd.com/read/28468593/hyaluronan-binding-peptide-for-targeting-peritoneal-carcinomatosis
#11
Hideki Ikemoto, Prakash Lingasamy, Anne-Mari Anton Willmore, Hedi Hunt, Kaarel Kurm, Olav Tammik, Pablo Scodeller, Lorena Simón-Gracia, Venkata Ramana Kotamraju, Andrew M Lowy, Kazuki N Sugahara, Tambet Teesalu
Peritoneal carcinomatosis results from dissemination of solid tumors in the peritoneal cavity, and is a common site of metastasis in patients with carcinomas of gastrointestinal or gynecological origin. Peritoneal carcinomatosis treatment is challenging as poorly vascularized, disseminated peritoneal micro-tumors are shielded from systemic anticancer drugs and drive tumor regrowth. Here, we describe the identification and validation of a tumor homing peptide CKRDLSRRC (IP3), which upon intraperitoneal administration delivers payloads to peritoneal metastases...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28460635/transcriptomic-profiling-and-quantitative-high-throughput-qhts-drug-screening-of-cdh1-deficient-hereditary-diffuse-gastric-cancer-hdgc-cells-identify-treatment-leads-for-familial-gastric-cancer
#12
Ina Chen, Lesley Mathews-Greiner, Dandan Li, Abisola Abisoye-Ogunniyan, Satyajit Ray, Yansong Bian, Vivek Shukla, Xiaohu Zhang, Raj Guha, Craig Thomas, Berkley Gryder, Athina Zacharia, Joal D Beane, Sarangan Ravichandran, Marc Ferrer, Udo Rudloff
BACKGROUND: Patients with hereditary diffuse gastric cancer (HDGC), a cancer predisposition syndrome associated with germline mutations of the CDH1 (E-cadherin) gene, have few effective treatment options. Despite marked differences in natural history, histopathology, and genetic profile to patients afflicted by sporadic gastric cancer, patients with HDGC receive, in large, identical systemic regimens. The lack of a robust preclinical in vitro system suitable for effective drug screening has been one of the obstacles to date which has hampered therapeutic advances in this rare disease...
May 1, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28442943/flow-shear-stress-enhances-the-proliferative-potential-of-cultured-radial-glial-cells-possibly-via-an-activation-of-mechanosensitive-calcium-channel
#13
Min Gu Park, Heeyeong Jang, Sang-Hoon Lee, C Justin Lee
Radial glial cells (RGCs) which function as neural stem cells are known to be non-excitable and their proliferation depends on the intracellular calcium (Ca(2+)) level. It has been well established that Inositol 1,4,5-trisphosphate (IP3)-mediated Ca(2+) release and Ca(2+) entry through various Ca(2+) channels are involved in the proliferation of RGCs. Furthermore, RGCs line the ventricular wall and are exposed to a shear stress due to a physical contact with the cerebrospinal fluid (CSF). However, little is known about how the Ca(2+) entry through mechanosensitive ion channels affects the proliferation of RGCs...
April 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/28435065/influence-of-er-leak-on-resting-cytoplasmic-ca-2-and-receptor-mediated-ca-2-signalling-in-human-macrophage
#14
Janice A Layhadi, Samuel J Fountain
Mechanisms controlling endoplasmic reticulum (ER) Ca(2+) homeostasis are important regulators of resting cytoplasmic Ca(2+) concentration ([Ca(2+)]cyto) and receptor-mediated Ca(2+) signalling. Here we investigate channels responsible for ER Ca(2+) leak in THP-1 macrophage and human primary macrophage. In the absence of extracellular Ca(2+) we employ ionomycin action at the plasma membrane to stimulate ER Ca(2+) leak. Under these conditions ionomycin elevates [Ca(2+)]cyto revealing a Ca(2+) leak response which is abolished by thapsigargin...
April 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28424618/pharmacological-and-biochemical-characterization-of-tlqp-21-activation-of-a-binding-site-on-cho-cells
#15
Laura Molteni, Laura Rizzi, Elena Bresciani, Roberta Possenti, Pamela Petrocchi Passeri, Corrado Ghè, Giampiero Muccioli, Jean-Alain Fehrentz, Pascal Verdié, Jean Martinez, Robert J Omeljaniuk, Giuseppe Biagini, Anna Binda, Ilaria Rivolta, Vittorio Locatelli, Antonio Torsello
VGF is a propeptide of 617 amino acids expressed throughout the central and the peripheral nervous system. VGF and peptides derived from its processing have been found in dense core vesicles and are released from neuronal and neuroendocrine cells via the regulated secretory pathway. Among VGF-derived neuropeptides, TLQP-21 (VGF(556-576)) has raised a huge interest and is one of most studied. TLQP-21 is a multifunctional neuropeptide involved in the control of several physiological functions, potentially including energy homeostasis, pain modulation, stress responsiveness and reproduction...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28416699/ip3-mediated-gating-mechanism-of-the-ip3-receptor-revealed-by-mutagenesis-and-x-ray-crystallography
#16
Kozo Hamada, Hideyuki Miyatake, Akiko Terauchi, Katsuhiko Mikoshiba
The inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) is an IP3-gated ion channel that releases calcium ions (Ca(2+)) from the endoplasmic reticulum. The IP3-binding sites in the large cytosolic domain are distant from the Ca(2+) conducting pore, and the allosteric mechanism of how IP3 opens the Ca(2+) channel remains elusive. Here, we identify a long-range gating mechanism uncovered by channel mutagenesis and X-ray crystallography of the large cytosolic domain of mouse type 1 IP3R in the absence and presence of IP3 Analyses of two distinct space group crystals uncovered an IP3-dependent global translocation of the curvature α-helical domain interfacing with the cytosolic and channel domains...
May 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28414037/spatio-temporal-regulation-of-connexin43-phosphorylation-and-gap-junction-dynamics
#17
REVIEW
Joell L Solan, Paul D Lampe
Gap junctions are specialized membrane domains containing tens to thousands of intercellular channels. These channels permit exchange of small molecules (<1000Da) including ions, amino acids, nucleotides, metabolites and secondary messengers (e.g., calcium, glucose, cAMP, cGMP, IP3) between cells. The common reductionist view of these structures is that they are composed entirely of integral membrane proteins encoded by the 21 member connexin human gene family. However, it is clear that the normal physiological function of this structure requires interaction and regulation by a variety of proteins, especially kinases...
April 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28413806/ryanodine-and-ip3-receptor-mediated-calcium-signaling-play-a-pivotal-role-in-neurological-infrared-laser-modulation
#18
Gleb P Tolstykh, Cory A Olsovsky, Bennett L Ibey, Hope T Beier
Pulsed infrared (IR) laser energy has been shown to modulate neurological activity through both stimulation and inhibition of action potentials. While the mechanism(s) behind this phenomenon is (are) not completely understood, certain hypotheses suggest that the rise in temperature from IR exposure could activate temperature- or pressure-sensitive ion channels or create pores in the cellular outer membrane, allowing an influx of typically plasma-membrane-impermeant ions. Studies using fluorescent intensity-based calcium ion ([Formula: see text]) sensitive dyes show changes in [Formula: see text] levels after various IR stimulation parameters, which suggests that [Formula: see text] may originate from the external solution...
April 2017: Neurophotonics
https://www.readbyqxmd.com/read/28413728/mechanism-of-endothelial-nitric-oxide-synthase-phosphorylation-and-activation-by-tentacle-extract-from-the-jellyfish-cyanea-capillata
#19
Beilei Wang, Dan Liu, Chao Wang, Qianqian Wang, Hui Zhang, Guoyan Liu, Xia Tao, Liming Zhang
Our previous study demonstrated that tentacle extract (TE) from the jellyfish Cyanea capillata (C. capillata) could cause a weak relaxation response mediated by nitric oxide (NO) using isolated aorta rings. However, the intracellular mechanisms of TE-induced vasodilation remain unclear. Thus, this study was conducted to examine the role of TE on Akt/eNOS/NO and Ca(2+) signaling pathways in human umbilical vein endothelial cells (HUVECs). Our results showed that TE induced dose- and time-dependent increases of eNOS activity and NO production...
2017: PeerJ
https://www.readbyqxmd.com/read/28412354/role-of-gpr30-in-estrogen-induced-prostate-epithelial-apoptosis-and-benign-prostatic-hyperplasia
#20
Deng-Liang Yang, Jia-Wen Xu, Jian-Guo Zhu, Yi-Lin Zhang, Jian-Bang Xu, Qing Sun, Xiao-Nian Cao, Wu-Lin Zuo, Ruo-Shui Xu, Jie-Hong Huang, Fu-Neng Jiang, Yang-Jia Zhuo, Bai-Quan Xiao, Yun-Zhong Liu, Dong-Bo Yuan, Zhao-Lin Sun, Hui-Chan He, Zhao-Rong Lun, Wei-De Zhong, Wen-Liang Zhou
Several studies have implicated estrogen and the estrogen receptor (ER) in the pathogenesis of benign prostatic hyperplasia (BPH); however, the mechanism underlying this effect remains elusive. In the present study, we demonstrated that estrogen (17β-estradiol, or E2)-induced activation of the G protein-coupled receptor 30 (GPR30) triggered Ca(2+) release from the endoplasmic reticulum, increased the mitochondrial Ca(2+) concentration, and thus induced prostate epithelial cell (PEC) apoptosis. Both E2 and the GPR30-specific agonist G1 induced a transient intracellular Ca(2+) release in PECs via the phospholipase C (PLC)-inositol 1, 4, 5-triphosphate (IP3) pathway, and this was abolished by treatment with the GPR30 antagonist G15...
April 12, 2017: Biochemical and Biophysical Research Communications
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