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https://www.readbyqxmd.com/read/28644030/a-plc-%C3%AE-1-feedback-pathway-regulates-lck-substrate-phosphorylation-at-the-t-cell-receptor-and-slp-76-complex
#1
Judson Belmont, Tao Gu, Ashley Marie Mudd, Arthur R Salomon
Phospholipase C gamma 1 (PLC-γ1) occupies a critically important position in the T cell signaling pathway. While its functions as a regulator of both Ca2+ signaling and PKC-family kinases are well characterized, PLC-γ1's role in the regulation of early T cell receptor signaling events is incompletely understood. Activation of the T cell receptor leads to the formation of a signalosome complex between SLP-76, LAT, PLC-γ1, Itk, and Vav1. Recent studies have revealed the existence of both positive and negative feedback pathways from SLP-76 to the apical kinase in the pathway, Lck...
June 23, 2017: Journal of Proteome Research
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/28498501/ppar-gamma-agonist-pioglitazone-modifies-craving-intensity-and-brain-white-matter-integrity-in-patients-with-primary-cocaine-use-disorder-a-double-blind-randomized-controlled-pilot-trial
#3
Joy M Schmitz, Charles E Green, Khader M Hasan, Jessica Vincent, Robert Suchting, Michael F Weaver, F Gerard Moeller, Ponnada A Narayana, Kathryn A Cunningham, Kelly T Dineley, Scott D Lane
BACKGROUND AND AIMS: Pioglitazone (PIO), a potent agonist of PPAR-gamma, is a promising candidate treatment for cocaine use disorder (CUD). We tested the effects of PIO on targeted mechanisms relevant to CUD: cocaine craving and brain white matter (WM) integrity. Feasibility, medication compliance, and tolerability were evaluated. DESIGN: Two-arm double-blind randomized controlled proof-of-concept pilot trial of PIO or placebo (PLC). SETTING: Single-site outpatient treatment research clinic in Houston, Texas, USA...
May 12, 2017: Addiction
https://www.readbyqxmd.com/read/28396398/selective-entrainment-of-gamma-subbands-by-different-slow-network-oscillations
#4
Weiwei Zhong, Mareva Ciatipis, Thérèse Wolfenstetter, Jakob Jessberger, Carola Müller, Simon Ponsel, Yevgenij Yanovsky, Jurij Brankačk, Adriano B L Tort, Andreas Draguhn
Theta oscillations (4-12 Hz) are thought to provide a common temporal reference for the exchange of information among distant brain networks. On the other hand, faster gamma-frequency oscillations (30-160 Hz) nested within theta cycles are believed to underlie local information processing. Whether oscillatory coupling between global and local oscillations, as showcased by theta-gamma coupling, is a general coding mechanism remains unknown. Here, we investigated two different patterns of oscillatory network activity, theta and respiration-induced network rhythms, in four brain regions of freely moving mice: olfactory bulb (OB), prelimbic cortex (PLC), parietal cortex (PAC), and dorsal hippocampus [cornu ammonis 1 (CA1)]...
April 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28363866/interferon-induces-interleukin-8-and-bone-marrow-stromal-cell-antigen-2-expression-inhibiting-the-production-of-hepatitis-b-virus-surface-antigen-from-human-hepatocytes
#5
Yuki Haga, Tatsuo Kanda, Shingo Nakamoto, Masato Nakamura, Reina Sasaki, Shuang Wu, Osamu Yokosuka
Hepatitis B virus (HBV) surface antigen (HBsAg) loss is one of the treatment goals of chronic HBV infection. Bone marrow stromal cell antigen 2 (BST2) is one of the interferon (IFN)-stimulated genes (ISGs) and inhibits the release of various enveloped viruses. Here we examined the effects of antiviral treatment on HBsAg levels and its intracellular mechanism in HBsAg-producing hepatocytes. In PLC/PRF/5 and Huh1, IFNα-2a treatment decreased HBsAg levels in their conditioned media. Upregulation of interleukin 8 (IL8), toll-like receptor 2 (TLR2) and interferon gamma-induced protein 10 (IP10) mRNAs was associated with the reduction of HBsAg in both PLC/PRF/5 and Huh1...
May 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28174090/targeting-trk-family-proteins-in-cancer
#6
REVIEW
Yekaterina B Khotskaya, Vijaykumar R Holla, Anna F Farago, Kenna R Mills Shaw, Funda Meric-Bernstam, David S Hong
The tropomyosin receptor kinase (TRK) family includes TRKA, TRKB, and TRKC proteins, which are encoded by NTRK1, NTRK2 and NTRK3 genes, respectively. Binding of neurotrophins to TRK proteins induces receptor dimerization, phosphorylation, and activation of the downstream signaling cascades via PI3K, RAS/MAPK/ERK, and PLC-gamma. TRK pathway aberrations, including gene fusions, protein overexpression, and single nucleotide alterations, have been implicated in the pathogenesis of many cancer types, with NTRK gene fusions being the most well validated oncogenic events to date...
February 4, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28063403/lat-alleviates-th2-treg-imbalance-in-an-ova-induced-allergic-asthma-mouse-model-through-lat-plc-%C3%AE-1-interaction
#7
Xi Chen, Xiao-Ming Li, Wen Gu, Di Wang, Yi Chen, Xue-Jun Guo
INTRODUCTION: Low expression of linker for activation of T cells (LAT) is observed in asthma. LAT and its downstream regulator, phospholipase C-gamma 1 (PLC-γ1) play important roles in the T cell antigen receptor signaling pathway, and their interaction is associated with CD4(+) cell polarization. Here, we investigated whether LAT can alleviate the imbalance among CD4(+) cell subgroups and the possible mechanism. METHODS: An ovalbumin-induced allergic asthma mouse model was established and LAT plasmid was delivered...
March 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/27894895/molecular-characterization-and-expression-analysis-of-olive-flounder-paralichthys-olivaceus-phospholipase-c-gamma-1-and-gamma-2
#8
Soo Ji Woo, Hyae In Jo, Hyung Ho Lee, Joon Ki Chung
Phospholipase C gamma 1 and gamma 2 (PLCG1 and PLCG2) are influential in modulating Ca(2+) and diacylglycerol, second messengers involved in tyrosine kinase-dependent signaling, including growth factor activation. Here, we used RACE (rapid amplification of cDNA ends) to clone cDNA encoding PLCG1 (PoPLCG1) and PLCG2 (PoPLCG2) in the olive flounder (Paralichthys olivaceus). The respective 1313 and 1249 amino acid sequences share high identity with human PLCG1 and PLCG2, and contain the following domains: pleckstrin homology (PH), EF-hand, catalytic X and Y, Src homology 2 (SH2), Src homology 3 (SH3), and C2...
April 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27598116/atractylodin-inhibits-interleukin-6-by-blocking-npm-alk-activation-and-mapks-in-hmc-1
#9
Hee-Sung Chae, Young-Mi Kim, Young-Won Chin
Atractylodin is one of the major constituents of the rhizome of Atractylodes lancea, which is widely used in Korean traditional medicine as a remedy for the treatment of gastritis and gastric ulcers. Despite of a major constituent of widely used botanical to treat inflammatory responses little is known about anti-inflammatory effect of atractylodin in the human mast cell (HMC-1). Hence, we evaluated the effect of atractylodin on the release of IL-6, the involvement of nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) and mitogen-activated protein kinases (MAPKs) in phorbol-12-myristate-13-acetate and A23187-induced HMC-1...
September 2, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27308350/vegf-signaling-mtor-complexes-and-the-endoplasmic-reticulum-towards-a-role-of-metabolic-sensing-in-the-regulation-of-angiogenesis
#10
Evdoxia Karali, Sofia Bellou, Dimitris Stellas, Apostolos Klinakis, Carol Murphy, Theodore Fotsis
Vascular endothelial growth factor (VEGF) activates unfolded protein response sensors in the endoplasmic reticulum through phospholipase C gamma (PLCγ)-mediated crosstalk with mammalian target of rapamycin complex 1 (mTORC1). Activation of transcription factor 6 (ATF6) and protein kinase RNA-like endoplasmic reticulum kinase (PERK) activate mTORC2, ensuring maximal endothelial cell survival and angiogenic activity through phosphorylation of AKT on Ser473. As mTORC1 is a metabolic sensor, metabolic signals may be integrated with signals from VEGF in the regulation of angiogenesis...
July 2014: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/27213427/porcine-circovirus-type-2-activates-cammk%C3%AE-to-initiate-autophagy-in-pk-15-cells-by-increasing-cytosolic-calcium
#11
Yuanxing Gu, Baozhu Qi, Yingshan Zhou, Xiaowu Jiang, Xian Zhang, Xiaoliang Li, Weihuan Fang
Porcine circovirus type 2 (PCV2) induces autophagy via the 5' adenosine monophosphate-activated protein kinase (AMPK)/extracellular signal-regulated kinase (ERK)/tuberous sclerosis complex 2 (TSC2)/mammalian target of rapamycin (mTOR) pathway in pig kidney PK-15 cells. However, the underlying mechanisms of AMPK activation in autophagy induction remain unknown. With specific inhibitors and RNA interference (RNAi), we show that PCV2 infection upregulated calcium/calmodulin-dependent protein kinase kinase-beta (CaMKKβ) by increasing cytosolic Ca(2+) via inositol 1,4,5-trisphosphate receptor (IP3R)...
2016: Viruses
https://www.readbyqxmd.com/read/26527801/cish-actively-silences-tcr-signaling-in-cd8-t-cells-to-maintain-tumor-tolerance
#12
Douglas C Palmer, Geoffrey C Guittard, Zulmarie Franco, Joseph G Crompton, Robert L Eil, Shashank J Patel, Yun Ji, Nicholas Van Panhuys, Christopher A Klebanoff, Madhusudhanan Sukumar, David Clever, Anna Chichura, Rahul Roychoudhuri, Rajat Varma, Ena Wang, Luca Gattinoni, Francesco M Marincola, Lakshmi Balagopalan, Lawrence E Samelson, Nicholas P Restifo
Improving the functional avidity of effector T cells is critical in overcoming inhibitory factors within the tumor microenvironment and eliciting tumor regression. We have found that Cish, a member of the suppressor of cytokine signaling (SOCS) family, is induced by TCR stimulation in CD8(+) T cells and inhibits their functional avidity against tumors. Genetic deletion of Cish in CD8(+) T cells enhances their expansion, functional avidity, and cytokine polyfunctionality, resulting in pronounced and durable regression of established tumors...
November 16, 2015: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/26403151/metabotropic-gabab-receptors-mediate-gaba-inhibition-of-acetylcholine-release-in-the-rat-neuromuscular-junction
#13
Artem I Malomouzh, Konstantin A Petrov, Leniz F Nurullin, Evgeny E Nikolsky
Gamma-aminobutyric acid (GABA) is an amino acid which acts as a neurotransmitter in the central nervous system. Here, we studied the effects of GABA on non-quantal, spontaneous, and evoked quantal acetylcholine (ACh) release from motor nerve endings. We found that while the application of 10 μM of GABA had no effect on spontaneous quantal ACh release, as detected by the frequency of miniature endplate potentials, GABA reduced the non-quantal ACh release by 57%, as determined by the H-effect value. Finally, the evoked quantal ACh release, estimated by calculating the quantal content of full-sized endplate potentials (EPPs), was reduced by 34%...
December 2015: Journal of Neurochemistry
https://www.readbyqxmd.com/read/26351666/rapid-and-transient-palmitoylation-of-the-tyrosine-kinase-lck-mediates-fas-signaling
#14
Askar M Akimzhanov, Darren Boehning
Palmitoylation is the posttranslational modification of proteins with a 16-carbon fatty acid chain through a labile thioester bond. The reversibility of protein palmitoylation and its profound effect on protein function suggest that this modification could play an important role as an intracellular signaling mechanism. Evidence that palmitoylation of proteins occurs with the kinetics required for signal transduction is not clear, however. Here we show that engagement of the Fas receptor by its ligand leads to an extremely rapid and transient increase in palmitoylation levels of the tyrosine kinase Lck...
September 22, 2015: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/26291058/wisp-2-in-human-gastric-cancer-and-its-potential-metastatic-suppressor-role-in-gastric-cancer-cells-mediated-by-jnk-and-plc-%C3%AE-pathways
#15
Jiafu Ji, Shuqin Jia, Yongning Jia, Ke Ji, Rachel Hargest, Wen G Jiang
BACKGROUND: It has recently been shown that WISP proteins (Wnt-inducted secreted proteins), a group of intra- and extra-cellular regulatory proteins, have been implicated in the initiation and progression of a variety of tumour types including colorectal and breast cancer. However, the role of WISP proteins in gastric cancer (GC) cells and their clinical implications have not yet been elucidated. METHODS: The expression of WISP molecules in a cohort of GC patients was analysed using real-time quantitative PCR and immunohistochemistry...
September 15, 2015: British Journal of Cancer
https://www.readbyqxmd.com/read/26289587/endogenous-bdnf-augments-nmda-receptor-phosphorylation-in-the-spinal-cord-via-plc%C3%AE-pkc-and-pi3k-akt-pathways-during-colitis
#16
Miao Liu, Jarren C Kay, Shanwei Shen, Li-Ya Qiao
BACKGROUND: Spinal central sensitization is an important process in the generation and maintenance of visceral hypersensitivity. The release of brain-derived neurotrophic factor (BDNF) from the primary afferent neurons to the spinal cord contributes to spinal neuronal plasticity and increases neuronal activity and synaptic efficacy. The N-Methyl-D-aspartic acid (NMDA) receptor possesses ion channel properties, and its activity is modulated by phosphorylation of its subunits including the NMDA receptor 1 (NR1)...
August 20, 2015: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/26271970/-mutation-of-palmitoylation-site-of-linker-for-activation-of-t-cells-inhibits-signal-transduction-mediated-by-glycosyl-phosphatidyl-inositol-anchored-cd59-in-t-cells
#17
Meihua Gao, Lina Wang, Bing Wang, Beibei Cong, Shuchao Zhang
OBJECTIVE: To construct the lentivirus carrying the mutated palmitoylation site of the linker for activation of T cells (LAT) and infect Jurkat cells with it to establish stable cell line, and to investigate the effect of LAT palmitoylation mutation on T cell signaling induced by CD59. METHODS: Negative control (neg-EGFP) and LAT-M-EGFP fusion protein gene vectors were respectively constructed and then packaged using lentivirus. Subsequently, Jurkat cells were infected with them to establish stable cell lines...
August 2015: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/26126534/orally-administered-mucolytic-drug-l-carbocisteine-inhibits-angiogenesis-and-tumor-growth-in-mice
#18
Tomohiro Shinya, Tsubasa Yokota, Shiori Nakayama, Sayuri Oki, Junpei Mutoh, Satoru Takahashi, Keizo Sato
Angiogenesis, the formation of new blood vessels from pre-existing vessels, is essential for the growth and metastasis of tumors. In this study, we found that l-carbocisteine, a widely used expectorant, potently inhibits angiogenesis in vitro and in vivo. An in vivo Matrigel plug assay revealed that l-carbocisteine (2.5 mg/kg i.p. twice daily) significantly inhibited vascular endothelial growth factor (VEGF)-induced angiogenesis. l-Carbocisteine also suppressed VEGF-stimulated proliferation, migration, and formation of capillary-like structures of human umbilical vein endothelial cells (HUVECs)...
September 2015: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/26034173/the-importance-of-il-6-in-the-development-of-lat-mediated-autoimmunity
#19
Sarah A O'Brien, Minghua Zhu, Weiguo Zhang
Linker for activation of T cells (LAT) is a transmembrane adaptor protein that is highly tyrosine phosphorylated upon engagement of the TCR. Phosphorylated LAT binds Grb2, Gads, and phospholipase C (PLC)γ1 to mediate T cell activation, proliferation, and cytokine production. T cells from mice harboring a mutation at the PLCγ1 binding site of LAT (Y136F) have impaired calcium flux and Erk activation. Interestingly, these T cells are highly activated, resulting in the development of a lymphoproliferative syndrome in these mice...
July 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/25978952/aqueous-extract-of-orostachys-japonicus-a-berger-exerts-immunostimulatory-activity-in-raw-264-7-macrophages
#20
Hye-Jin Park, Hye Jeong Yang, Ki Hyun Kim, Sang Hee Kim
ETHNOPHARMACOLOGICAL RELEVANCE: Orostachys japonicus A. Berger (Crassulaceae) (OJ), well-known as Wa-song in Korea is a medicinal plant with immunoregulatory, anti-febrile, antidote, and anti-cancer activities. This study was aimed at evaluating the immunostimulatory effect of O. japonicus A. Berger and its possible mechanisms of action. MATERIALS AND METHODS: To evaluate the effect of OJ aqueous extract on macrophage activity, we evaluated the modulation of macrophage activation state by observing structural (phagocytic activities) and the production of nitric oxide increase...
July 21, 2015: Journal of Ethnopharmacology
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