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Phospholipase C gamma 2

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...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Chloë De Witte, Christian Schulz, Annemieke Smet, Peter Malfertheiner, Freddy Haesebrouck
This article aimed to review the literature from 2015 dealing with gastric and enterohepatic non-Helicobacter pylori Helicobacter species (NHPH). A summary of the gastric microbiota interactions with H. pylori is also presented. An extensive number of studies were published during the last year and have led to a better understanding of the pathogenesis of infections with NHPH. These infections are increasingly reported in human patients, including infections with H. cinaedi, mainly characterized by severe bacteremia...
September 2016: Helicobacter
Alvaro Alvarez, Raúl Lagos-Cabré, Milene Kong, Areli Cárdenas, Francesca Burgos-Bravo, Pascal Schneider, Andrew F G Quest, Lisette Leyton
Our previous reports indicate that ligand-induced αVβ3 integrin and Syndecan-4 engagement increases focal adhesion formation and migration of astrocytes. Additionally, ligated integrins trigger ATP release through unknown mechanisms, activating P2X7 receptors (P2X7R), and the uptake of Ca(2+) to promote cell adhesion. However, whether the activation of P2X7R and ATP release are required for astrocyte migration and whether αVβ3 integrin and Syndecan-4 receptors communicate with P2X7R via ATP remains unknown...
September 2016: Biochimica et Biophysica Acta
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
Y Fujioka, A Stahlberg, M Ochi, K Olmarker
PURPOSE: To determine the expression of inflammation- and pain-related genes at days 1 and 3 in the dorsal root ganglion (DRG) of rats with or without disc puncture, using real-time quantitative polymerase chain reaction (RT-qPCR) with the TaqMan low-density array (TLDA). METHODS: 53 female Sprague-Dawley rats were used. The left facet joint between L4 and L5 was removed, and the DRG and intervertebral disc between the vertebrae were exposed. The L4-5 intervertebral disc was punctured using a 0...
April 2016: Journal of Orthopaedic Surgery
Hong Xu, Li-Na Gu, Qian-Yuan Yang, De-Yu Zhao, Feng Liu
Mast cells play a pivotal role in the immediate reaction in asthma. In a previous study, it was found that MicroRNA-221 (miR-221) was associated with asthma. Hence, in the present study, the role and the potential mechanisms of miR-221 on immunoglobulin E (IgE)-mediated activation of mast cells degranulation were investigated. MiR-221 expression was first quantified by qRT-PCR in IgE-mediated activation of mast cells. RBL-2H3 cells were then transfected with miR-221 mimic or miR-221 inhibitor, the IgE-mediated degranulation was detected in mast cells...
June 2016: Journal of Bioenergetics and Biomembranes
Zhao Yin, Hai-Jiang Xu, Xia-Li Yao, Gang Liu, Chun-Jie Nie, Han Wei, Cai Li, Ming-Lu Liang, Zhang-Yin Ming, Xiao-Jian Zhang
AIMS: It has been proven that carbon nanoparticles or diesel exhaust particles stimulate platelet activation. However, the effect of fine particle matter (PM2.5 ) on platelet activation remains unknown, which motivates this study. METHODS: PM2.5 samples were collected in an urban area of Zhengzhou, China. To study the morphological characteristics and the mass concentrations of trace elements of PM2.5 samples, a filed-emission scanning electron microscope, the Image-J software, and an inductively coupled plasma mass spectrometry were used...
April 4, 2016: Environmental Toxicology
Jennifer Gossmann, Manfred Stolte, Michael Lohoff, Philipp Yu, Roland Moll, Florian Finkernagel, Holger Garn, Cornelia Brendel, Alwina Bittner, Andreas Neubauer, Minh Q Huynh
Gastric mucosa-associated lymphoid tissue (MALT) lymphomas develop from a chronic Helicobacter infection. Phospholipase C gamma 2 (PLCG2) is important for B-cell survival and proliferation. We used BALB/c mice with a gain-of-function mutation in the Plcg2 gene (Ali5) to analyze its role in the development of gastric MALT lymphoma. Heterozygous BALB/c Plcg2Ali5/+ and wildtype (WT) mice were infected with Helicobacter felis (H. felis) and observed up to 16 months for development of gastric MALT lymphomas. In contrast to our initial hypothesis, Plcg2Ali5/+ mice developed MALT lymphomas less frequently than their WT littermates after long-term infection of 16 months...
2016: PloS One
Y Poorna Chandra Rao, P Pavan Kumar, B R Lokesh
Industrially produced partially hydrogenated vegetable fat (PHVF) contains trans fatty acids (TFA) mostly comprising elaidic acid (EA, 18:1∆9t). Though, the harmful effects of TFA on health have been repeatedly publicized, the fat containing TFA have been continued to be used as a cooking medium in many regions of the world. The adverse effects of PHVF on oxidative stress and inflammatory markers and the possible ameliorative action of rice bran oil (RBO) on these markers were evaluated. Weaning rats were fed a AIN-93 purified diet supplemented with the following lipids: groundnut oil (GNO, 10 wt%), PHVF (10 wt%), RBO (10 wt%), PHVF blended with RBO at 2...
April 2016: Lipids
Chunmei Xia, Shanwei Shen, Fiza Hashmi, Li-Ya Qiao
Patients with inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS) often experience increased sensory responsiveness in the urinary bladder reflecting neurogenic bladder overactivity. Here we demonstrate that colitis-induced up-regulation of the phospholipase C gamma (PLCγ) pathway downstream of brain-derived neurotrophic factor (BDNF) in bladder afferent neurons in the dorsal root ganglia (DRG) plays essential roles in activating these neurons thereby leading to bladder hyperactivity. Upon induction of colitis with 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats, we found that the phosphorylation (activation) level of cAMP responsive element-binding (p-CREB) protein, a molecular switch of neuronal plasticity, was increased in specifically labeled bladder afferent neurons in the thoracolumbar and lumbosacral DRGs...
December 11, 2015: Experimental Neurology
Corinne E Decker, Zhengfeng Yang, Ryan Rimer, Kyung-Hyun Park-Min, Claudia Macaubas, Elizabeth D Mellins, Deborah V Novack, Roberta Faccio
Phospholipase C gamma-2 (PLCγ2)-dependent calcium (Ca(2+)) oscillations are indispensable for nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) activation and downstream gene transcription driving osteoclastogenesis during skeletal remodeling and pathological bone loss. Here we describe, to our knowledge, the first known function of transmembrane protein 178 (Tmem178), a PLCγ2 downstream target gene, as a critical modulator of the NFATc1 axis. In surprising contrast to the osteopetrotic phenotype of PLCγ2(-/-) mice, Tmem178(-/-) mice are osteopenic in basal conditions and are more susceptible to inflammatory bone loss, owing to enhanced osteoclast formation...
December 22, 2015: Proceedings of the National Academy of Sciences of the United States of America
Yukinori Kozuma, Tetsuya Yamamoto, Eiichi Ishikawa, Fumiyo Yoshida, Hiroyoshi Akutsu, Masahide Matsuda, Kei Nakai, Wataro Tsuruta, Shingo Takano, Akira Matsumura, Haruhiko Ninomiya
BACKGROUND: Appropriate hemostasis is essential for clear visualization of the neural structures and cleavage planes. It is also essential for avoiding heat-induced injury, minimizing blood loss, and reducing operative time. OBJECTIVE: To determine the role of cerebrospinal fluid (CSF) in platelet-dependent hemostasis during neurosurgery. METHODS: The amplification of aggregation, activation of integrin αIIbβ3, intrinsic and extrinsic coagulation pathways, and activation of signaling cascades in platelets were evaluated...
February 2016: Neurosurgery
Ana Saavedra, Mar Puigdellívol, Shiraz Tyebji, Pradeep Kurup, Jian Xu, Silvia Ginés, Jordi Alberch, Paul J Lombroso, Esther Pérez-Navarro
Brain-derived neurotrophic factor (BDNF) promotes synaptic strengthening through the regulation of kinase and phosphatase activity. Conversely, striatal-enriched protein tyrosine phosphatase (STEP) opposes synaptic strengthening through inactivation or internalization of signaling molecules. Here, we investigated whether BDNF regulates STEP levels/activity. BDNF induced a reduction of STEP61 levels in primary cortical neurons, an effect that was prevented by inhibition of tyrosine kinases, phospholipase C gamma, or the ubiquitin-proteasome system (UPS)...
August 2016: Molecular Neurobiology
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
Ta-Ming Liu, Jennifer A Woyach, Yiming Zhong, Arletta Lozanski, Gerard Lozanski, Shuai Dong, Ethan Strattan, Amy Lehman, Xiaoli Zhang, Jeffrey A Jones, Joseph Flynn, Leslie A Andritsos, Kami Maddocks, Samantha M Jaglowski, Kristie A Blum, John C Byrd, Jason A Dubovsky, Amy J Johnson
Ibrutinib has significantly improved the outcome of patients with relapsed chronic lymphocytic leukemia (CLL). Recent reports attribute ibrutinib resistance to acquired mutations in Bruton agammaglobulinemia tyrosine kinase (BTK), the target of ibrutinib, as well as the immediate downstream effector phospholipase C, γ2 (PLCG2). Although the C481S mutation found in BTK has been shown to disable ibrutinib's capacity to irreversibly bind this primary target, the detailed mechanisms of mutations in PLCG2 have yet to be established...
July 2, 2015: Blood
David Gilad, Sharon Shorer, Maya Ketzef, Alon Friedman, Israel Sekler, Elias Aizenman, Michal Hershfinkel
The aim of this study was to investigate the role of the synaptic metabotropic zinc receptor mZnR/GPR39 in physiological adaptation to epileptic seizures. We previously demonstrated that synaptic activation of mZnR/GPR39 enhances inhibitory drive in the hippocampus by upregulating neuronal K(+)/Cl(-) co-transporter 2 (KCC2) activity. Here, we first show that mZnR/GPR39 knockout (KO) adult mice have dramatically enhanced susceptibility to seizures triggered by a single intraperitoneal injection of kainic acid, when compared to wild type (WT) littermates...
September 2015: Neurobiology of Disease
Sreeja B Asokan, Heath E Johnson, Anisur Rahman, Samantha J King, Jeremy D Rotty, Irina P Lebedeva, Jason M Haugh, James E Bear
Chemotaxis, migration toward soluble chemical cues, is critical for processes such as wound healing and immune surveillance and is exhibited by various cell types, from rapidly migrating leukocytes to slow-moving mesenchymal cells. To study mesenchymal chemotaxis, we observed cell migration in microfluidic chambers that generate stable gradients of platelet-derived growth factor (PDGF). Surprisingly, we found that pathways implicated in amoeboid chemotaxis, such as PI3K and mammalian target of rapamycin signaling, are dispensable for PDGF chemotaxis...
December 22, 2014: Developmental Cell
Eun-Hee Park, Jung-Min Kim, Kyung-Mi Kim, Dawon Kang, Young-Ah Cho, Jun-Young Choi, Jea-Young Song, Hyung-Lyun Kang, Woo-Kon Lee, Myung-Je Cho, Kwang-Ho Rhee, Ji-Hyun Seo, Hee-Shang Youn, Seung-Chul Baik
In our previous study, γ-glutamyl transpeptidase (GGT) isolated from Helicobacter pylori induced apoptosis of AGS cells. Here, we investigate Ca(2+) effects on GGT-induced apoptosis. The GGT transiently and significantly increased intracellular Ca(2+) concentration ([Ca(2+)]i) in AGS cells in a dose-dependent manner (P < 0.05). The GGT-induced Ca(2+) increase resulted from Ca(2+) influx and release through the phospholipase C - inositol 1,4,5-trisphosphate (PLC-IP3) pathway. The GGT-induced apoptosis was significantly reduced by treatment with U73122 (a PLC inhibitor) and xestospongin (an IP3 receptor antagonist) (P < 0...
December 2014: Canadian Journal of Microbiology
T M Schnöder, P Arreba-Tutusaus, I Griehl, L Bullinger, M Buschbeck, S W Lane, K Döhner, C Plass, D B Lipka, F H Heidel, T Fischer
Erythropoiesis is a tightly regulated process. Development of red blood cells occurs through differentiation of hematopoietic stem cells (HSCs) into more committed progenitors and finally into erythrocytes. Binding of erythropoietin (Epo) to its receptor (EpoR) is required for erythropoiesis as it promotes survival and late maturation of erythroid progenitors. In vivo and in vitro studies have highlighted the requirement of EpoR signaling through Janus kinase 2 (Jak2) tyrosine kinase and Stat5a/b as a central pathway...
June 2015: Cell Death and Differentiation
Susan Li, Christine H Miller, Eugenia Giannopoulou, Xiaoyu Hu, Lionel B Ivashkiv, Baohong Zhao
Osteoclastogenesis requires activation of RANK signaling as well as costimulatory signals from immunoreceptor tyrosine-based activation motif-containing (ITAM-containing) receptors/adaptors, predominantly tyrosine kinase-binding proteins DAP12 and FcRγ, in osteoclast precursors. It is not well understood how costimulatory signals are regulated and integrated with RANK signaling. Here, we found that osteopetrotic bone phenotypes in mice lacking DAP12 or DAP12 and FcRγ are mediated by the transcription factor RBP-J, as deletion of Rbpj in these mice substantially rescued the defects of bone remodeling...
November 2014: Journal of Clinical Investigation
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