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https://www.readbyqxmd.com/read/28434079/cell-culture-complications-due-to-mechanical-release-of-atp-and-activation-of-purinoceptors
#1
REVIEW
Geoffrey Burnstock, Gillian E Knight
There is abundant evidence that ATP (adenosine 5'-triphosphate) is released from a variety of cultured cells in response to mechanical stimulation. The release mechanism involved appears to be a combination of vesicular exocytosis and connexin and pannexin hemichannels. Purinergic receptors on cultured cells mediate both short-term purinergic signalling of secretion and long-term (trophic) signalling such as proliferation, migration, differentiation and apoptosis. We aim in this review to bring to the attention of non-purinergic researchers using tissue culture that the release of ATP in response to mechanical stress evoked by the unavoidable movement of the cells acting on functional purinergic receptors on the culture cells is likely to complicate the interpretation of their data...
April 22, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28432149/cd73-on-t-cells-orchestrates-cardiac-wound-healing-after-myocardial-infarction-by-purinergic-metabolic-reprogramming
#2
Nadine Borg, Christina Alter, Nicole Görldt, Christoph Jacoby, Zhaoping Ding, Bodo Steckel, Christine Quast, Florian Bönner, Daniela Friebe, Sebastian Temme, Ulrich Flögel, Jürgen Schrader
Background -T-cells are required for proper healing after myocardial infarction. The mechanism of their beneficial action, however, is unknown. The pro-inflammatory "danger signal" adenosine triphosphate (ATP), released from damaged cells, is degraded by the ectonucleotidases CD39 and CD73 to the anti-inflammatory mediator adenosine. Here, we investigate the contribution of CD73-derived adenosine produced by T-cells to cardiac remodeling after ischemia/reperfusion and define its mechanism of action. Methods -Myocardial ischemia (50 min /reperfusion) was induced in global CD73(-/-) and CD4-CD73(-/-) mice...
April 21, 2017: Circulation
https://www.readbyqxmd.com/read/28429411/nanodiscs-for-inpharma-nmr-characterization-of-gpcrs-ligand-binding-to-the-human-a2a-adenosine-receptor
#3
Kai Fredriksson, Philip Lottmann, Sonja Hinz, Iounut Onila, Aliaksei Shymanets, Christian Harteneck, Christa E Müller, Christian Griesinger, Thomas E Exner
G-protein-coupled-receptors (GPCRs) are of fundamental importance for signal transduction through cell membranes. This makes them important drug targets, but structure-based drug design (SBDD) is still hampered by the limitations for structure determination of unmodified GPCRs. We show that the interligand NOEs for pharmacophore mapping (INPHARMA) method can provide valuable information on ligand poses inside the binding site of the unmodified human A2A adenosine receptor reconstituted in nanodiscs. By comparing experimental INPHARMA spectra with back-calculated spectra based on ligand poses obtained from molecular dynamics simulations, a complex structure for A2A R with the low-affinity ligand 3-pyrrolidin-1-ylquinoxalin-2-amine was determined based on the X-ray structure of ligand ZM-241,358 in complex with a modified A2A R...
April 21, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28427397/hvc1-ameliorates-hyperlipidemia-and-inflammation-in-ldlr-mice
#4
Se-Yun Cheon, Kyung-Sook Chung, Kyung-Jin Lee, Ho-Young Choi, In-Hye Ham, Dong-Hoon Jung, Yun-Yeop Cha, Hyo-Jin An
BACKGROUND: HVC1 consists of Coptidis Rhizoma (dried rhizome of Coptischinensis), Scutellariae Radix (root of Scutellariabaicalensis), Rhei Rhizoma (rhizome of Rheum officinale), and Pruni Cortex (cortex of Prunusyedoensis Matsum). Although the components are known to be effective in various conditions such as inflammation, hypertension, and hypercholesterolemia, there are no reports of the molecular mechanism of its hypolipidemic effects. METHODS: We investigated the hypolipidemic effect of HVC1 in low-density lipoprotein receptor-deficient (LDLR(-/-)) mice fed a high-cholesterol diet for 13 weeks...
April 20, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28427099/role-of-phosphodiesterases-on-the-function-of-aryl-hydrocarbon-receptor-interacting-protein-aip-in-the-pituitary-gland-and-on-the-evaluation-of-aip-gene-variants
#5
Laura C Hernández-Ramírez, Giampaolo Trivellin, Constantine A Stratakis
Familial isolated pituitary adenoma (FIPA) is caused in about 20% of cases by loss-of-function germline mutations in the AIP gene. Patients harboring AIP mutations usually present with somatotropinomas resulting either in gigantism or young-onset acromegaly. AIP encodes for a co-chaperone protein endowed with tumor suppressor properties in somatotroph cells. Among other mechanisms proposed to explain this function, a regulatory effect over the 3',5'-cyclic adenosine monophosphate (cAMP) signaling pathway seems to play a prominent role...
April 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28426203/tyrosine-kinase-activation-and-conformational-flexibility-lessons-from-src-family-tyrosine-kinases
#6
Yilin Meng, Matthew P Pond, Benoît Roux
Protein kinases are enzymes that catalyze the covalent transfer of the γ-phosphate of an adenosine triphosphate (ATP) molecule onto a tyrosine, serine, threonine, or histidine residue in the substrate and thus send a chemical signal to networks of downstream proteins. They are important cellular signaling enzymes that regulate cell growth, proliferation, metabolism, differentiation, and migration. Unregulated protein kinase activity is often associated with a wide range of diseases, therefore making protein kinases major therapeutic targets...
April 20, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28425039/disaggregation-following-agonist-induced-platelet-activation-in-patients-on-dual-antiplatelet-therapy
#7
Patricia P Wadowski, Beate Eichelberger, Christoph W Kopp, Joseph Pultar, Daniela Seidinger, Renate Koppensteiner, Irene M Lang, Simon Panzer, Thomas Gremmel
Disaggregation as the difference between maximal and final platelet aggregation by light transmission aggregometry indicates the stability of platelet aggregates. We evaluated the extent of disaggregation after platelet stimulation with adenosine diphosphate (ADP), arachidonic acid (AA), collagen, epinephrine, and thrombin receptor-activating peptide (TRAP)-6 in 323 patients on dual antiplatelet therapy with daily aspirin and clopidogrel (group 1), prasugrel (group 2), or ticagrelor (group 3) therapy. All patients in group 1 underwent elective angioplasty and stenting, whereas all patients included in groups 2 and 3 suffered from acute coronary syndromes (STEMI or NSTEMI) and underwent urgent PCI...
April 19, 2017: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/28424924/effects-of-gw002-a-novel-recombinant-human-glucagon-like-peptide-1-glp-1-analog-fusion-protein-on-cho-recombinant-cells-and-bks-db-mice
#8
Wan-Wan Ji, Dong-An Yu, Min Fan, Meng You, You Lu, Er-Bing Li, Ning Xie, Shou-Sheng Yan
AIMS: GLP-1-based strategies have many advantages in treatment of type 2 diabetes mellitus (T2DM), but native GLP-1 has a short half-life in the circulation, which limits its clinical application. The purpose of this study was to evaluate the effects of GW002, a novel recombinant GLP-1 analog fusion protein produced by linking the human GLP-1 analog C-terminus to the N-terminus of human serum albumin via a linker, in vitro and in BKS-db mice. METHODS: To determine whether GW002 can activate the GLP-1 receptor in cells, the level of luciferase expression was evaluated in vitro...
April 19, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28423583/the-protection-of-meloxicam-against-chronic-aluminium-overload-induced-liver-injury-in-rats
#9
Yang Yang, Qin He, Hong Wang, Xinyue Hu, Ying Luo, Guojuan Liang, Shengnan Kuang, Shaoshan Mai, Jie Ma, Xiaoyan Tian, Qi Chen, Junqing Yang
The present study was designed to observe the protective effect and mechanisms of meloxicam on liver injury caused by chronic aluminium exposure in rats. The histopathology was detected by hematoxylin-eosin staining. The levels of prostaglandin E2, cyclic adenosine monophosphate and inflammatory cytokines were detected by enzyme linked immunosorbent assay. The expressions of cyclooxygenases-2, prostaglandin E2 receptors and protein kinase A were measured by western blotting and immunohistochemistry. Our experimental results showed that aluminium overload significantly damaged the liver...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421534/immune-alterations-in-cd8-t-cells-are-associated-with-neuronal-c-c-and-c-x-c-chemokine-receptor-regulation-through-adenosine-a2a-receptor-signaling-in-a-btbr-t-itpr3-tf-j-autistic-mouse-model
#10
Sheikh F Ahmad, Mushtaq A Ansari, Ahmed Nadeem, Saleh A Bakheet, Raish Mohammad, Sabry M Attia
Associative studies on a range of neurodevelopmental disorders have identified relationships between behavioral deficits and immune system function. The BTBR T(+) Itpr3(tf)/J (BTBR) mouse strain displays aberrant characteristics in its social behavior and immune responses, providing a significant opportunity to examine the relationship between behavior and the immune system. This study investigated the influence of adenosine A2A receptor activity on C-C and C-X-C chemokine receptors involved in autism in the BTBR mouse model...
April 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28420694/caffeine-preferentially-protects-against-oxygen-induced-retinopathy
#11
Shuya Zhang, Rong Zhou, Bo Li, Haiyan Li, Yanyan Wang, Xuejiao Gu, Lingyun Tang, Cun Wang, Dingjuan Zhong, Yuanyuan Ge, Yuqing Huo, Jing Lin, Xiao-Ling Liu, Jiang-Fan Chen
Retinopathy of prematurity (ROP) is the leading cause of childhood blindness, but current anti-VEGF therapy is concerned with delayed retinal vasculature, eye, and brain development of preterm infants. The clinical observation of reduced ROP severity in premature infants after caffeine treatment for apnea suggests that caffeine may protect against ROP. Here, we demonstrate that caffeine did not interfere with normal retinal vascularization development but selectively protected against oxygen-induced retinopathy (OIR) in mice...
April 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28420163/beneficial-effects-of-melatonin-on-the-in-vitro-maturation-of-sheep-oocytes-and-its-relation-to-melatonin-receptors
#12
Xiuzhi Tian, Feng Wang, Lu Zhang, Changjiu He, Pengyun Ji, Jing Wang, Zhenzhen Zhang, Dongying Lv, Wusiman Abulizi, Xuguang Wang, Zhengxing Lian, Guoshi Liu
(1) Background: The binding sites of melatonin, as a multifunctional molecule, have been identified in human, porcine, and bovine samples. However, the binding sites and mechanisms of melatonin have not been reported in sheep; (2) Methods: Cumulus-oocyte complexes (COCs) were cultured in TCM-199 supplemented with melatonin at concentrations of 0, 10(-3), 10(-5), 10(-7), 10(-9), and 10(-11) M. Melatonin receptors (MT1 and MT2) were evaluated via immunofluorescence and Western blot. The effects of melatonin on cumulus cell expansion, nuclear maturation, embryo development, and related gene (GDF9, DNMT1, PTX3, HAS2, and EGFR) expression were investigated...
April 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28419419/the-isoprenoid-derivative-n6-benzyladenosine-cm223-exerts-antitumor-effect-in-glioma-patient-derived-primary-cells-through-the-mevalonate-pathway
#13
Elena Ciaglia, Manuela Grimaldi, Mario Abate, Mario Scrima, Manuela Rodriquez, Chiara Laezza, Roberta Ranieri, Simona Pisanti, Pierangela Ciuffreda, Clementina Manera, Patrizia Gazzerro, Anna Maria D'Ursi, Maurizio Bifulco
BACKGROUND AND PURPOSE: N6-Isopentenyladenosine (i6A) is a modified nucleoside exerting in vitro and in vivo antiproliferative effects. We previously demonstrated that the i6A action is correlated to farnesyl pyrophosphate synthase (FPPS) expression and activity, a key enzyme involved in the mevalonate (MVA) pathway, which is found aberrant in brain cancer. To develop new anti-glioma strategies, we looked for other valuable compounds exhibiting improved activity as compared to i6A. EXPERIMENTAL APPROACH: we designed and synthesized i6A derivatives characterized by the introduction of diverse chemical moieties in the N6 position of adenosine and tested for their efficacy in U87 and primary derived patient's glioma cell model...
April 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28418405/adenosine-a2a-receptor-and-erk-driven-impulsivity-potentiates-hippocampal-neuroblast-proliferation
#14
A Oliveros, C H Cho, A Cui, S Choi, D Lindberg, D Hinton, M-H Jang, D-S Choi
Dampened adenosine A2A receptor (A2AR) function has been implicated in addiction through enhancement of goal-directed behaviors. However, the contribution of the A2AR to the control of impulsive reward seeking remains unknown. Using mice that were exposed to differential reward of low rate (DRL) schedules during Pavlovian-conditioning, second-order schedule discrimination, and the 5-choice serial reaction time task (5-CSRTT), we demonstrate that deficits of A2AR function promote impulsive responses. Antagonism of the A2AR lowered ERK1 and ERK2 phosphorylation in the dorsal hippocampus (dHip) and potentiated impulsivity during Pavlovian-conditioning and the 5-CSRTT...
April 18, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28417934/expression-of-adenosine-a2b-receptor-and-adenosine-deaminase-in-rabbit-gastric-mucosa-ecl-cells
#15
Rosa María Arin, Ana Isabel Vallejo, Yuri Rueda, Olatz Fresnedo, Begoña Ochoa
Adenosine is readily available to the glandular epithelium of the stomach. Formed continuously in intracellular and extracellular locations, it is notably produced from ATP released in enteric cotransmission. Adenosine analogs modulate chloride secretion in gastric glands and activate acid secretion in isolated parietal cells through A2B adenosine receptor (A2BR) binding. A functional link between surface A2BR and adenosine deaminase (ADA) was found in parietal cells, but whether this connection is a general feature of gastric mucosa cells is unknown...
April 12, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28416823/-identification-of-a-new-pro-invasion-factor-in-tumor-microenvironment-progress-in-function-and-mechanism-of-extracellular-atp
#16
W G Fang, X X Tian
Up to 90% of all cancer related morbidity and mortality can be attributed to metastasis. In recent years the study of tumor microenvironment, its cellular and molecular components, and how they can affect neoplastic progression toward metastasis, has become a hot focus in cancer research. Accumulated evidence shows that the formation of metastasis is a multi-step sequential process, in which, the tumor cells continuously interact with the host microenvironment. Host derived factors, i.e. growth factors/inhibitors, angiogenic factors, chemokines, etc...
April 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/28415676/nitrobenzylthioinosine-mimics-adenosine-to-attenuate-the-epileptiform-discharge-of-hippocampal-neurons-from-epileptic-rats
#17
Hao Huang, Jing Wang, Jun Zhang, Zhong Luo, Dongxu Li, Xiaowei Qiu, Yan Peng, Zhongxiang Xu, Ping Xu, Zucai Xu
Nitrobenzylthioinosine (NBTI), a specific inhibitor of type 1 equilibrative nucleoside transporter, could regulate the extracellular adenosine concentration and have protective roles in seizures. However, the protection mechanism of NBTI in seizures remains poorly understood. Here, the expression pattern and subcellular distribution of adenosine A1 receptor were detected by Western blot analysis and double-labeling immunofluorescence staining in Lithium Chloride-Pilocarpine induced epileptic rat model. At 24 h after pilocarpine induced rat seizures, hippocampal slices were prepared and the evoked excitatory postsynaptic currents (eEPSCs) amplitude of pyramidal neurons in hippocampus CA1 region was recorded using whole-cell patch clamp...
March 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415673/camp-pka-creb-bdnf-signaling-pathway-in-hippocampus-mediates-cyclooxygenase-2-induced-learning-memory-deficits-of-rats-subjected-to-chronic-unpredictable-mild-stress
#18
Ying Luo, Shengnan Kuang, Huan Li, Dongzhi Ran, Junqing Yang
To investigate the mechanism of cyclooxygenase 2 (COX2) in learning and memory impairments in rats subjected to chronic unpredictable mild stress (CUMS), meloxicam was used intragastrically to inhibit the activity of cyclooxygenase 2. Moreover, cyclooxygenase 2 over-expressing or RNA interfere lentivirus was injected intraventricularly to increase or decrease the enzyme's expression, respectively. The body weights and sucrose consumption were used to analyze depressive behaviors, while the Morris water maze and step-down-type passive avoidance tests were carried out to evaluate the learning-memory functions...
March 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415011/design-and-synthesis-of-novel-xanthine-derivatives-as-potent-and-selective-a2b-adenosine-receptor-antagonists-for-the-treatment-of-chronic-inflammatory-airway-diseases
#19
Sujay Basu, Dinesh A Barawkar, Vidya Ramdas, Meena Patel, Yogesh Waman, Anil Panmand, Santosh Kumar, Sachin Thorat, Minakshi Naykodi, Arnab Goswami, B Srinivasa Reddy, Vandna Prasad, Sandhya Chaturvedi, Azfar Quraishi, Suraj Menon, Shalini Paliwal, Abhay Kulkarni, Vikas Karande, Indraneel Ghosh, Syed Mustafa, Siddhartha De, Vaibhav Jain, Ena Ray Banerjee, Sreekanth R Rouduri, Venkata P Palle, Anita Chugh, Kasim A Mookhtiar
Adenosine induces bronchial hyperresponsiveness and inflammation in asthmatics through activation of A2B adenosine receptor (A2BAdoR). Selective antagonists have been shown to attenuate airway reactivity and improve inflammatory conditions in pre-clinical studies. Hence, the identification of novel, potent and selective A2BAdoR antagonist may be beneficial for the potential treatment of asthma and Chronic Obstructive Pulmonary Disease (COPD). Towards this effort, we explored several prop-2-ynylated C8-aryl or heteroaryl substitutions on xanthine chemotype and found that 1-prop-2-ynyl-1H-pyrazol-4-yl moiety was better tolerated at the C8 position...
April 12, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28412965/multireceptor-fingerprints-in-progressive-supranuclear-palsy
#20
Wang Zheng Chiu, Laura Donker Kaat, Agnita J W Boon, Wouter Kamphorst, Axel Schleicher, Karl Zilles, John C van Swieten, Nicola Palomero-Gallagher
BACKGROUND: Progressive supranuclear palsy (PSP) with a frontal presentation, characterized by cognitive deficits and behavioral changes, has been recognized as an early clinical picture, distinct from the classical so-called Richardson and parkinsonism presentations. The midcingulate cortex is associated with executive and attention tasks and has consistently been found to be impaired in imaging studies of patients with PSP. The aim of the present study was to determine alterations in neurotransmission underlying the pathophysiology of PSP, as well as their significance for clinically identifiable PSP subgroups...
April 17, 2017: Alzheimer's Research & Therapy
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