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https://www.readbyqxmd.com/read/28924009/site-specific-regulation-of-p2x7-receptor-function-in-microglia-gates-morphine-analgesic-tolerance
#1
Heather Leduc-Pessah, Nicholas L Weilinger, Churmy Y Fan, Nicole E Burma, Roger J Thompson, Tuan Trang
Tolerance to the analgesic effects of opioids is a major problem in chronic pain management. Microglia are implicated in opioid tolerance, but the core mechanisms regulating their response to opioids remain obscure. By selectively ablating microglia in the spinal cord using a saporin-conjugated antibody to Mac1, we demonstrate a causal role for microglia in the development, but not maintenance, of morphine tolerance in male rats. Increased P2X7 receptor (P2X7R) activity is a cardinal feature of microglial activation, and in this study we found that morphine potentiates P2X7R-mediated Ca(2+) responses in resident spinal microglia acutely isolated from morphine tolerant rats...
September 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28910941/-effects-of-src-on-cervical-cancer-cells-proliferation-and-apoptosis-through-erk-signal-transduction-pathway
#2
Z C Song, L Ding, Z Y Ren, X S Sun, Q Yang, L Wang, M J Feng, C L Liu, J T Wang
Objective: To explore the effect of Src on cervical cancer cells through ERK signal transduction pathway. Methods: Experimental study was carried out in vitro. Cervical cancer cell lines Hela (HPV-positive) and C33A (HPV-negative) were treated with Src kinase inhibitor PP2. Then, the cell cycle and apoptosis of each group were evaluated by using flow cytometry (FCM). Western blotting and Real-time PCR were used to detect the levels of the expression of ERK 1/2, c-Fos and c-Jun mRNA and protein respectively...
September 10, 2017: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
https://www.readbyqxmd.com/read/28893976/teaching-an-old-drug-new-tricks-agonism-antagonism-and-biased-signaling-of-pilocarpine-through-m3-muscarinic-acetylcholine-receptor
#3
Alexey Pronin, Qiang Wang, Vladlen Z Slepak
Pilocarpine is a prototypical drug used to treat glaucoma and dry mouth and classified as either a full or partial muscarinic agonist. Here, we report several unexpected results pertaining to its interaction with muscarinic M3 receptor (M3R). We found that pilocarpine was 1,000 times less potent in stimulating mouse eye pupil constriction than muscarinic agonists oxotremorin-M (Oxo-M) or carbachol (CCh), even though all three ligands have similar Kd values for M3R. In contrast to CCh or Oxo-M, pilocarpine does not induce Ca2+ mobilization via endogenous M3R in HEK293T or mouse insulinoma MIN6 cells...
September 11, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28890980/fast-and-accurate-prediction-of-proton-affinities-revisiting-the-extended-koopmans-theorem-for-protons
#4
Laura Pedraza-González, Jorge Charry, William Quintero, Jorge Alí-Torres, Andrés Reyes
In this work we propose schemes based on the extended Koopmans' theorem for quantum nuclei (eKT), in the framework of the any particle molecular orbital approach (APMO/KT), for the quantitative prediction of gas phase proton affinities (PAs). The performance of these schemes has been tested on a set of 300 organic molecules containing diverse functional groups. The APMO/KT scheme scaled by functional group (APMO/KT-SC-FG) displays an overall mean absolute error of 1.1 kcal mol(-1) with respect to experimental data...
September 11, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28879169/herpes-simplex-virus-type-1-neuronal-infection-perturbs-golgi-apparatus-integrity-through-activation-of-src-tyrosine-kinase-and-dyn-2-gtpase
#5
Carolina Martin, Luis Leyton, Melissa Hott, Yennyfer Arancibia, Carlos Spichiger, Mark A McNiven, Felipe A Court, Margarita I Concha, Patricia V Burgos, Carola Otth
Herpes simplex virus type 1 (HSV-1) is a ubiquitous pathogen that establishes a latent persistent neuronal infection in humans. The pathogenic effects of repeated viral reactivation in infected neurons are still unknown. Several studies have reported that during HSV-1 epithelial infection, the virus could modulate diverse cell signaling pathways remodeling the Golgi apparatus (GA) membranes, but the molecular mechanisms implicated, and the functional consequences to neurons is currently unknown. Here we report that infection of primary neuronal cultures with HSV-1 triggers Src tyrosine kinase activation and subsequent phosphorylation of Dynamin 2 GTPase, two players with a role in GA integrity maintenance...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28855900/dt-13-ameliorates-tnf-%C3%AE-induced-vascular-endothelial-hyperpermeability-via-non-muscle-myosin-iia-and-the-src-pi3k-akt-signaling-pathway
#6
Yuanyuan Zhang, Yuwei Han, Yazheng Zhao, Yanni Lv, Yang Hu, Yisha Tan, Xueyuan Bi, Boyang Yu, Junping Kou
DT-13(25(R,S)-ruscogenin-1-O-[β-d-glucopyranosyl-(1→2)][β-d-xylopyranosyl-(1→3)]-β-d-fucopyranoside) has been identified as an important factor in TNF-α-induced vascular inflammation. However, the effect of DT-13 on TNF-α-induced endothelial permeability and the potential molecular mechanisms remain unclear. Hence, this study was undertaken to elucidate the protective effect of DT-13 on TNF-α-induced endothelial permeability and the underlying mechanisms in vivo and in vitro. The in vivo results showed that DT-13 could ameliorate endothelial permeability in mustard oil-induced plasma leakage in the skin and modulate ZO-1 organization...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28855588/morphine-activation-of-mu-opioid-receptors-causes-disinhibition-of-neurons-in-the-ventral-tegmental-area-mediated-by-%C3%AE-arrestin2-and-c-src
#7
Fiona A Bull, Daniel T Baptista-Hon, Jeremy J Lambert, Wendy Walwyn, Tim G Hales
The tyrosine kinase, c-Src, participates in mu opioid receptor (MOP) mediated inhibition in sensory neurons in which β-arrestin2 (β-arr2) is implicated in its recruitment. Mice lacking β-arr2 exhibit increased sensitivity to morphine reinforcement; however, whether β-arr2 and/or c-Src participate in the actions of opioids in neurons within the reward pathway is unknown. It is also unclear whether morphine acts exclusively through MOPs, or involves delta opioid receptors (DOPs). We examined the involvement of MOPs, DOPs, β-arr2 and c-Src in the inhibition by morphine of GABAergic inhibitory postsynaptic currents (IPSCs) recorded from neurons in the mouse ventral tegmental area...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28851829/glucocorticoids-promote-von-hippel-lindau-degradation-and-hif-1%C3%AE-stabilization
#8
Andrea Vettori, David Greenald, Garrick K Wilson, Margherita Peron, Nicola Facchinello, Eleanor Markham, Mathavan Sinnakaruppan, Laura C Matthews, Jane A McKeating, Francesco Argenton, Fredericus J M van Eeden
Glucocorticoid (GC) and hypoxic transcriptional responses play a central role in tissue homeostasis and regulate the cellular response to stress and inflammation, highlighting the potential for cross-talk between these two signaling pathways. We present results from an unbiased in vivo chemical screen in zebrafish that identifies GCs as activators of hypoxia-inducible factors (HIFs) in the liver. GCs activated consensus hypoxia response element (HRE) reporters in a glucocorticoid receptor (GR)-dependent manner...
August 29, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28836688/src-kinase-inhibition-reduces-inflammatory-and-cytoskeletal-changes-in-%C3%AE-f508-human-cholangiocytes-and-improves-cftr-correctors-efficacy
#9
Romina Fiorotto, Mariangela Amenduni, Valeria Mariotti, Luca Fabris, Carlo Spirli, Mario Strazzabosco
CFTR, the channel mutated in cystic fibrosis (CF), is expressed by the biliary epithelium (i.e cholangiocytes) of the liver. Progressive clinical liver disease (CFLD) occurs in about 10% of CF patients and represents the third leading cause of death. Impaired secretion and inflammation contribute to CFLD, however the lack of human-derived experimental models has hampered the understanding of CFLD pathophysiology and the search for a cure. We have investigated the cellular mechanisms altered in human CF cholangiocytes using induced pluripotent stem cells (iPSC) derived from healthy controls and a ΔF508 CFTR patient...
July 24, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28820778/src-kinase-inhibition-attenuates-morphine-tolerance-without-affecting-reinforcement-or-psychomotor-stimulation
#10
Fiona A Bull, Daniel T Baptista-Hon, Claire Sneddon, Lisa Wright, Wendy Walwyn, Tim G Hales
BACKGROUND: Prolonged opioid administration leads to tolerance characterized by reduced analgesic potency. Pain management is additionally compromised by the hedonic effects of opioids, the cause of their misuse. The multifunctional protein β-arrestin2 regulates the hedonic effects of morphine and participates in tolerance. These actions might reflect µ opioid receptor up-regulation through reduced endocytosis. β-Arrestin2 also recruits kinases to µ receptors. We explored the role of Src kinase in morphine analgesic tolerance, locomotor stimulation, and reinforcement in C57BL/6 mice...
August 18, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28819999/high-glucose-induces-hgf-independent-activation-of-met-receptor-in-human-renal-tubular-epithelium
#11
Lucia Mesarosova, Peter Ochodnicky, Jaklien C Leemans, Sandrine Florquin, Peter Krenek, Jan Klimas
CONTEXT: The role of hepatocyte growth factor (HGF) in diabetic kidney damage remains controversial. OBJECTIVE: To test the hypothesis that high glucose levels activate pathways related to HGF and its receptor Met and that this could participate in glucose-induced renal cell damage. MATERIALS AND METHODS: HK2 cells, a human proximal tubule epithelial cell line, were stimulated with high glucose for 48 hours. Levels of pMet/Met, pEGFR/EGFR, pSTAT3/STAT3, pAkt/Akt and pERK1/2/ERK1/2 were studied by immunoblotting...
August 18, 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28804222/chemical-chaperone-of-endoplasmic-reticulum-stress-inhibits-epithelial-mesenchymal-transition-induced-by-tgf-%C3%AE-1-in-airway-epithelium-via-the-c-src-pathway
#12
Heung-Man Lee, Ju-Hyung Kang, Jae-Min Shin, Seoung-Ae Lee, Il-Ho Park
Epithelial-mesenchymal transition (EMT) is a biological process that allows epithelial cells to assume a mesenchymal cell phenotype. EMT is considered as a therapeutic target for several persistent inflammatory airway diseases related to tissue remodeling. Herein, we investigated the role of endoplasmic reticulum (ER) stress and c-Src in TGF-β1-induced EMT. A549 cells, primary nasal epithelial cells (PNECs), and inferior nasal turbinate organ cultures were exposed to 4-phenylbutylic acid (4PBA) or PP2 and then stimulated with TGF-β1...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28765886/exogenous-spermine-preserves-mitochondrial-bioenergetics-via-regulating-src-kinase-signaling-in-the-spinal-cord
#13
Rui Zhang, Xin-Nan Ma, Kai Liu, Lei Zhang, Meng Yao
Regulation of mitochondrial metabolism is becoming an important target in inhibiting necrosis and apoptosis following secondary spinal cord injury, and physiological compounds that reduce mitochondrial dysfunction are regarded as efficient protective reagents following injury. It has been demonstrated that spermine, a polyamine composed of four primary amines, may be taken up by a mitochondria‑specific uniporter and may preserve mitochondrial bioenergetics, suggesting that it may be important in the pathophysiology of mitochondria...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28764939/exercise-related-cognitive-effects-on-sensory-motor-control-in-athletes-and-drummers-compared-to-non-athletes-and-other-musicians
#14
V Bianco, M Berchicci, R L Perri, F Quinzi, F Di Russo
Both playing a musical instrument and playing sport produce brain adaptations that might affect sensory-motor functions. While the benefits of sport practice have traditionally been attributed to aerobic fitness, it is still unknown whether playing an instrument might induce similar brain adaptations, or if a specific musical instrument like drums might be associated to specific benefits because of its high energy expenditure. Since the aerobic costs of playing drums was estimated to be comparable to those of average sport activities, we hypothesized that these two groups might show both behavioral and neurocognitive similarities...
July 29, 2017: Neuroscience
https://www.readbyqxmd.com/read/28740236/reduced-expression-of-the-murine-hla-g-homolog-qa-2-is-associated-with-malignancy-epithelial-mesenchymal-transition-and-stemness-in-breast-cancer-cells
#15
Istéfani L da Silva, Lucía Montero-Montero, Ester Martín-Villar, Jorge Martin-Pérez, Bruno Sainz, Jaime Renart, Renata Toscano Simões, Émerson Soares Veloso, Cláudia Salviano Teixeira, Mônica C de Oliveira, Enio Ferreira, Miguel Quintanilla
Qa-2 is believed to mediate a protective immune response against cancer; however, little is known about the role of Qa-2 in tumorigenesis. Here, we used 4T1 breast cancer cells to study the involvement of Qa-2 in tumor progression in a syngeneic host. Qa-2 expression was reduced during in vivo tumor growth and in cell lines derived from 4T1-induced tumors. Tumor-derived cells elicited an epithelial-mesenchymal transition associated with upregulation of Zeb1 and Twist1/2 and enhanced tumor initiating and invasive capacities...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28736554/differential-requirements-for-src-family-kinases-in-syk-or-zap70-mediated-slp-76-phosphorylation-in-lymphocytes
#16
Frank Fasbender, Maren Claus, Sabine Wingert, Mina Sandusky, Carsten Watzl
In a synthetic biology approach using Schneider (S2) cells, we show that SLP-76 is directly phosphorylated at tyrosines Y113 and Y128 by SYK in the presence of ITAM-containing adapters such as CD3ζ, DAP12, or FcεRγ. This phosphorylation was dependent on at least one functional ITAM and a functional SH2 domain within SYK. Inhibition of Src-kinases by inhibitors PP1 and PP2 did not reduce SLP-76 phosphorylation in S2 cells, suggesting an ITAM and SYK dependent, but Src-kinase independent signaling pathway...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28729437/estradiol-induced-regulation-of-glut4-in-3t3-l1-cells-involvement-of-esr1-and-akt-activation
#17
Raquel Campello, Luciana Fátima, João Barreto-Andrade, Thais Fg Lucas, Rosana Cristina Tieko Mori, Catarina Segreti Porto, Ubiratan Fabres Machado
Impaired insulin-stimulated glucose uptake involves reduced expression of the GLUT4 (solute carrier family 2 facilitated glucose transporter member 4, SLC2A4 gene). 17β-estradiol (E2) modulates SLC2A4/GLUT4 expression, but the involved mechanisms are unclear. Although E2 exerts its biological effects by binding to estrogen receptors 1/2 (ESR1/2), which are nuclear transcriptional factors; extranuclear effects have also been proposed. We hypothesize that E2 regulates GLUT4 through a mechanism related to extranuclear ESR1...
July 20, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28673614/ros-dependent-activation-of-rhoa-rho-kinase-in-pulmonary-artery-role-of-src-family-kinases-and-arhgef1
#18
Charles E MacKay, Yasin Shaifta, Vladimir V Snetkov, Asvi A Francois, Jeremy P T Ward, Greg A Knock
The role of reactive oxygen species (ROS) in smooth muscle contraction is poorly understood. We hypothesised that G-protein coupled receptor (GPCR) activation and hypoxia induce Rho-kinase activity and contraction in rat intra-pulmonary artery (IPA) via stimulation of ROS production and subsequent Src-family kinase (SrcFK) activation. The T-type prostanoid receptor agonist U46619 induced ROS production in pulmonary artery smooth muscle cells (PASMC). U46619 also induced c-Src cysteine oxidation, SrcFK auto-phosphorylation, MYPT-1 and MLC20 phosphorylation and contraction in IPA, and all these responses were inhibited by antioxidants (ebselen, Tempol)...
September 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28670375/lyn-kinase-enhanced-hepatic-fibrosis-by-modulating-the-activation-of-hepatic-stellate-cells
#19
Yin Li, Lin Xiong, Jianping Gong
The non-selectivity of tyrosine kinase inhibitors is the leading cause of drug withdrawals, and limits their application in anti-fibrosis. The role of Src tyrosine kinase Lyn in hepatic fibrosis remains elusive. In this study, we aimed to elucidate the role of Lyn kinase in the pathogenesis of hepatic fibrosis. Through examining Lyn-transgenic (Lyn TG) mice treated with CCl4 (carbon tetrachloride), we determined whether Lyn kinase is involved in the pathogenesis of hepatic fibrosis. On top of that, we also investigated the role of Lyn in the activation of hepatic stellate cells (HSCs) in vitro...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28658050/effects-of-src-kinase-inhibition-on-expression-of-pro-caspase-2-after-brain-hypoxia-in-a-piglet-animal-model
#20
Dimitrios Angelis, Maria Delivoria-Papadopoulos
Caspase-2 has features of both initiator and effector caspases. Previously, we have shown that brain hypoxia-induced production of caspases 1, 3, 8, and 9 is Src kinase mediated, a nonreceptor intracellular family of kinases. The present study tests the hypothesis that hypoxia results in increased expression of caspase-2 and this effect is mediated by Src kinase. Two to three days old newborn piglets were subjected to normoxia, hypoxia (Hx, FiO2 7%), and Src kinase inhibition (using PP2, 1 mg/kg, intravenous), followed by 30 min of acute hypoxia (Hx+PP2)...
August 16, 2017: Neuroreport
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