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adenosine triphosphate

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https://www.readbyqxmd.com/read/27908642/negative-regulation-of-nlrp3-inflammasome-by-sirt1-in-vascular-endothelial-cells
#1
Yanxiang Li, Xiaofeng Yang, Yanhao He, Weirong Wang, Jiye Zhang, Wei Zhang, Ting Jing, Bo Wang, Rong Lin
NLRP3 inflammasome not only functions as a critical effector in innate immunity, but also triggers the production of proinflammatory cytokines involved in inflammation-associated diseases. Sirtuin 1 (SIRT1) plays an important role in the regulation of cellular inflammation. However, whether the activation of NLRP3 inflammasome is regulated by SIRT1 remains unknown. In this study, we investigated the regulatory effect of SIRT1 on NLRP3 inflammasome and the underlying mechanisms. We found that lipopolysaccharide (LPS) and adenosine triphosphate (ATP)-induced the activation of NLRP3 inflammasome in human umbilical vein endothelial cells (HUVECs)...
November 4, 2016: Immunobiology
https://www.readbyqxmd.com/read/27906627/oxidized-low-density-lipoproteins-enhance-expression-and-activity-of-cd39-and-cd73-in-the-human-aortic-valve-endothelium
#2
Ewa Kaniewska-Bednarczuk, Michał Mielcarek, Adrian H Chester, Ewa M Slominska, Magdi H Yacoub, Ryszard T Smolenski
Extracellular nucleotides regulate thrombosis, inflammation, and immune response. Ectonucleoside triphosphate diphosphohydrolase 1 (CD39) and ecto-5'-nucleotidase (CD73) convert extracellular nucleotides in a sequential order: ATP to ADP, AMP, and then to adenosine. In this study, we aimed to test an effect of oxidized low-density lipoprotein (ox-LDL) on CD39 and CD73 in endothelial cells. Human aortic valve endothelial cells were exposed to ox-LDL for 24-48 h. Next, the activity, protein expression, and mRNA transcripts level of CD39 and CD73 were characterized by an incubation with ATP or AMP followed by high-performance liquid chromatography analysis of media as well as western blots and qPCR...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27906624/influence-of-4-pyridone-3-carboxamide-1%C3%AE-d-ribonucleoside-4pyr-on-activities-of-extracellular-enzymes-in-endothelial-human-cells
#3
I Pelikant-Małecka, A Sielicka, E Kaniewska, R T Smoleński, E M Słomińska
Previous studies demonstrated that human endothelial cells were capable to phosphorylate 4-pyridone-3-carboxamide-1β-D-ribonucleoside (4PYR) to monophosphate (4PYMP) and formed another metabolite-an analog of NAD (4PYRAD). Elevated levels of 4PYMP and 4PYRAD had an adverse effect on energy balance-depressed adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD) concentration in human endothelial cells. Ecto-enzymes such as ecto-nucleoside triphosphate diphosphohydrolase (eNTPD); ecto-5'-nucleotidase (e5'NT); and ecto-adenosine deaminase (eADA) are involved in controlling of inflammation and platelet aggregation...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27906063/characterization-of-a-multiprotein-complex-involved-in-excitation-transcription-coupling-of-skeletal-muscle
#4
Manuel Arias-Calderón, Gonzalo Almarza, Alexis Díaz-Vegas, Ariel Contreras-Ferrat, Denisse Valladares, Mariana Casas, Héctor Toledo, Enrique Jaimovich, Sonja Buvinic
BACKGROUND: Electrical activity regulates the expression of skeletal muscle genes by a process known as "excitation-transcription" (E-T) coupling. We have demonstrated that release of adenosine 5'-triphosphate (ATP) during depolarization activates membrane P2X/P2Y receptors, being the fundamental mediators between electrical stimulation, slow intracellular calcium transients, and gene expression. We propose that this signaling pathway would require the proper coordination between the voltage sensor (dihydropyridine receptor, DHPR), pannexin 1 channels (Panx1, ATP release conduit), nucleotide receptors, and other signaling molecules...
April 11, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27902932/adenosine-triphosphate-analogs-can-efficiently-inhibit-the-zika-virus-rna-dependent-rna-polymerase
#5
Kamil Hercík, Jaroslav Kozak, Michal Šála, Milan Dejmek, Hubert Hřebabecký, Eva Zborníková, Miroslav Smola, Daniel Ruzek, Radim Nencka, Evzen Boura
We describe the expression and purification of an active recombinant Zika virus RNA-dependent RNA polymerase (RdRp). Next, we present the development and optimization of an in vitro assay to measure its activity. We then applied the assay to selected triphosphate analogs and discovered that 2'-C-methylated nucleosides exhibit strong inhibitory activity. Surprisingly, also carbocyclic derivatives with the carbohydrate locked in a North-like conformation as well as a ribonucleotide with a South conformation exhibited strong activity...
November 27, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27902447/a-unique-type-of-gsk-3-inhibitor-brings-new-opportunities-to-the-clinic
#6
Avital Licht-Murava, Rom Paz, Lilach Vaks, Limor Avrahami, Batya Plotkin, Miriam Eisenstein, Hagit Eldar-Finkelman
Development of protein kinase inhibitors is a focus of many drug discovery programs. A major problem, however, is the limited specificity of the commonly used adenosine triphosphate-competitive inhibitors and the weak inhibition of the more selective substrate-competitive inhibitors. Glycogen synthase kinase-3 (GSK-3) is a promising drug target for treating neurodegenerative disorders, including Alzheimer's disease (AD), but most GSK-3 inhibitors have not reached the clinic. We describe a new type of GSK-3 inhibitor, L807mts, that acts through a substrate-to-inhibitor conversion mechanism that occurs within the catalytic site of the enzyme...
November 15, 2016: Science Signaling
https://www.readbyqxmd.com/read/27901621/perfluorooctanoic-acid-induces-mitochondrial-dysfunction-in-mc3t3-e1-osteoblast-cells
#7
Eun Mi Choi, Kwang Sik Suh, Sang Youl Rhee, Seungjoon Oh, Jeong-Taek Woo, Sung Woon Kim, Young Seol Kim, Youngmi Kim Pak, Suk Chon
Perfluorooctanoic acid (PFOA), a stable organic perfluorinated compound, is an emerging persistent organic pollutant, found widely in human and wildlife populations. Recent evidence suggests that exposure to environmental toxicants can be associated with higher risks of osteoporosis and fractures. We studied the cellular toxicology of PFOA in MC3T3-E1osteoblast cells. To examine the effect of PFOA, we measured cell viability, reactive oxygen species (ROS), mitochondrial superoxide, and mitochondrial parameters including adenosine triphosphate (ATP) level, mitochondrial membrane potential (MMP), cardiolipin content, and cytochrome c release in MC3T3-E1 cells...
November 30, 2016: Journal of Environmental Science and Health. Part A, Toxic/hazardous Substances & Environmental Engineering
https://www.readbyqxmd.com/read/27899525/reactive-oxygen-species-induce-virus-independent-mavs-oligomerization-in-systemic-lupus-erythematosus
#8
Iwona A Buskiewicz, Theresa Montgomery, Elizabeth C Yasewicz, Sally A Huber, Michael P Murphy, Richard C Hartley, Ryan Kelly, Mary K Crow, Andras Perl, Ralph C Budd, Andreas Koenig
The increased expression of genes induced by type I interferon (IFN) is characteristic of viral infections and systemic lupus erythematosus (SLE). We showed that mitochondrial antiviral signaling (MAVS) protein, which normally forms a complex with retinoic acid gene I (RIG-I)-like helicases during viral infection, was activated by oxidative stress independently of RIG-I helicases. We found that chemically generated oxidative stress stimulated the formation of MAVS oligomers, which led to mitochondrial hyperpolarization and decreased adenosine triphosphate production and spare respiratory capacity, responses that were not observed in similarly treated cells lacking MAVS...
November 29, 2016: Science Signaling
https://www.readbyqxmd.com/read/27895802/vitamin-c-induces-apoptosis-in-ags-cells-via-production-of-ros-of-mitochondria
#9
Jae Young Lim, Donghyun Kim, Bok Ran Kim, Jin Su Jun, Jung Sook Yeom, Ji Sook Park, Ji-Hyun Seo, Chan Hoo Park, Hyang Ok Woo, Hee-Shang Youn, Seung-Chul Baik, Woo-Kon Lee, Myung-Je Cho, Kwang-Ho Rhee
It has been demonstrated that vitamin C exhibits anti-cancer activity in various tumor cell lines; however, its specific mechanism of action remains unknown. Although the diagnosis and therapy of cancer patients have markedly improved in recent years, safer and more cost-effective treatments are still required. Therefore, the present study examined the effect of vitamin C on the induction of cell death in gastric cancer and its underlying mechanism of action. It was observed that the cytotoxicity of vitamin C on the human gastric cancer cell line AGS is dependent on the apoptotic pathway, including caspase cascades, but not on the necroptotic pathway...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27895775/high-expression-of-cd39-in-gastric-cancer-reduces-patient-outcome-following-radical-resection
#10
Xiao-Yan Cai, Xue-Fei Wang, Jun Li, Jiang-Nan Dong, Jiang-Qi Liu, Neng-Ping Li, Bei Yun, Rong-Long Xia, Jing Qin, Yi-Hong Sun
Ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1), also known as cluster of differentiation (CD)39, is the rate-limiting enzyme in the generation of immunosuppressive adenosine and is important in tumor progression. The present study evaluated the expression of CD39(+) and CD39(+) forkhead box P3 (FoxP3)(+) regulatory T (Treg) cells in gastric cancer (GC), and determined their prognostic roles in patients with GC following radical resection. It was observed that CD39 was expressed at significantly higher rates in tumor tissues as compared with paired peritumoral tissues...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27893093/ligation-of-cd40-in-human-m%C3%A3-ller-cells-induces-p2x7-receptor-dependent-death-of-retinal-endothelial-cells
#11
Jose-Andres C Portillo, Yalitza Lopez Corcino, George R Dubyak, Timothy S Kern, Shigemi Matsuyama, Carlos S Subauste
Purpose: Cluster of differentiation 40 (CD40) is required for retinal capillary degeneration in diabetic mice, a process mediated by the retinal endothelial cells (REC) death. However, CD40 activates prosurvival signals in endothelial cells. The purpose of this study was to identify a mechanism by which CD40 triggers programmed cell death (PCD) of RECs and address this paradox. Methods: Human RECs and Müller cells were incubated with CD154 and L-N6-(1-Iminoethyl)lysine (L-Nil, nitric oxide synthase 2 inhibitor), α-lipoic acid (inhibitor of oxidative stress), anti-Fas ligand antibody, or A-438079 (P2X7 adenosine triphosphate [ATP] receptor inhibitor)...
November 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27885718/purinergic-receptors-new-targets-for-the-treatment-of-gout-and-fibrosis
#12
REVIEW
Thomas Gicquel, Brendan Le Daré, Elisabeth Boichot, Vincent Lagente
Adenosine triphosphate is involved in many metabolic reactions, but it has also a role as a cellular danger signal transmitted through purinergic receptors (PRs). Indeed, ATP can bind to PRs which are found in the membrane of many cell types, although the relative proportions of the receptor subtypes differ. PRs are classified according to genetic and pharmacological criteria and especially their affinities for agonists and their transduction mechanism (i.e. as metabotropic P2YRs or ionotropic P2XRs). Extracellular ATP release by activated or necrotic cells may activate various PRs and especially P2X7R, the best-characterized PR, on immune cells...
November 25, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27884343/increased-tolerance-to-stress-in-cardiac-expressed-gain-of-function-of-adenosine-triphosphate-sensitive-potassium-channel-subunit-kir6-1
#13
Matthew C Henn, M Burhan Janjua, Haixia Zhang, Evelyn M Kanter, Carol M Makepeace, Richard B Schuessler, Colin G Nichols, Jennifer S Lawton
BACKGROUND: The adenosine triphosphate-sensitive potassium (KATP) channel opener diazoxide (DZX) prevents myocyte volume derangement and reduced contractility secondary to stress. KATP channels are composed of pore-forming (Kir6.1 or Kir6.2) and regulatory (sulfonylurea receptor, SUR1 or SUR2) subunits. Gain of function (GOF) of Kir6.1 subunits has been implicated in cardiac pathology in Cantu syndrome in humans (cardiomegaly, lymphedema, and pericardial effusions). We hypothesized that GOF of Kir6...
December 2016: Journal of Surgical Research
https://www.readbyqxmd.com/read/27881823/nanobodies-that-block-gating-of-the-p2x7-ion-channel-ameliorate-inflammation
#14
Welbeck Danquah, Catherine Meyer-Schwesinger, Björn Rissiek, Carolina Pinto, Arnau Serracant-Prat, Miriam Amadi, Domenica Iacenda, Jan-Hendrik Knop, Anna Hammel, Philine Bergmann, Nicole Schwarz, Joana Assunção, Wendy Rotthier, Friedrich Haag, Eva Tolosa, Peter Bannas, Eric Boué-Grabot, Tim Magnus, Toon Laeremans, Catelijne Stortelers, Friedrich Koch-Nolte
Ion channels are desirable therapeutic targets, yet ion channel-directed drugs with high selectivity and few side effects are still needed. Unlike small-molecule inhibitors, antibodies are highly selective for target antigens but mostly fail to antagonize ion channel functions. Nanobodies-small, single-domain antibody fragments-may overcome these problems. P2X7 is a ligand-gated ion channel that, upon sensing adenosine 5'-triphosphate released by damaged cells, initiates a proinflammatory signaling cascade, including release of cytokines, such as interleukin-1β (IL-1β)...
November 23, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27881490/new-micellar-electrokinetic-chromatographic-method-for-analyzing-idebenone-in-pediatric-formulations
#15
Mario Contin, Fabián Buontempo, Cristian García Becerra, Cecilia Dobrecky, Silvia Lucangioli, Valeria Tripodi
A novel, simple and reliable method based on micellar electrokinetic chromatography with ultraviolet detection was developed to analyze idebenone in a pediatric formulation. Idebenone is a synthetic short chain benzoquinone that acts as an electron carrier in the mitochondrial electron transport chain facilitating the production of adenosine triphosphate. It can be found in two different redox states that differ in their physiological properties. Idebenone has been investigated as a treatment in several neurological disorders like Friedreich's ataxia, Leber's hereditary optic neuropathy, mitochondrial encephalomyopathies and senile dementia...
November 23, 2016: Journal of Chromatographic Science
https://www.readbyqxmd.com/read/27878881/beneficial-effect-of-extracellular-adenosine-5-triphosphate-treatment-on-the-indochinese-leopard-panthera-pardus-delacouri-sperm-quality-after-cryopreservation
#16
P Thuwanut, W Tipkantha, B Siriaroonrat, P Comizzoli, K Chatdarong
The Indochinese leopard (Panthera pardus delacouri) population, included in CITES Appendix I, has been declining for decades. Proper gamete preservation condition is critical for breeding programme management using artificial insemination or in vitro fertilization (IVF). The present study aimed at investigating the impact of post-thawing treatment of leopard semen with extracellular adenosine 5'-triphosphate (ATPe) on sperm quality (including morphological traits and ability to fertilize an oocyte). Semen from six adult male leopards was collected by electroejaculation (one ejaculation per cat)...
November 22, 2016: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/27876122/a-hypothesis-on-the-mechanism-of-action-of-high-dose-thyroid-in-refractory-mood-disorders
#17
Tammas Kelly
Multiple lines of evidence suggest the hypothesis that high dose thyroid therapy corrects for cellular hypothyroidism found in bipolar disorders. Evidence indicates that bipolar disorders are associated with mitochondrial dysfunction which results in low cellular adenosine 5'-triphosphate (ATP) levels. Transport of thyroid hormones into cells is energy intensive and dependent on ATP except in the pituitary gland. Inadequate ATP levels makes it difficult to get thyroid hormone into cells leading to cellular hypothyroidism...
December 2016: Medical Hypotheses
https://www.readbyqxmd.com/read/27875899/amelioration-of-energy-metabolism-by-melatonin-in-skeletal-muscle-of-rats-with-lps-induced-endotoxemia
#18
E Ozkok, H Yorulmaz, G Ates, A Aksu, N Balkis, Ö Şahin, S Tamer
In the literature, few studies have investigated the effects of melatonin on energy metabolism in skeletal muscle in endotoxemia. We investigated the effects of melatonin on tissue structure, energy metabolism in skeletal muscle, and antioxidant level of rats with endotoxemia. We divided rats into 4 groups, control, lipopolysaccharide (LPS) (20 mg/kg, i.p., single dose), melatonin (10 mg/kg, i.p., three times), and melatonin + LPS. Melatonin was injected i.p. 30 min before and after the 2nd and 4th hours of LPS injection...
November 23, 2016: Physiological Research
https://www.readbyqxmd.com/read/27872255/proteolipid-protein-deficient-myelin-promotes-axonal-mitochondrial-dysfunction-via-altered-metabolic-coupling
#19
Xinghua Yin, Grahame J Kidd, Nobuhiko Ohno, Guy A Perkins, Mark H Ellisman, Chinthasagar Bastian, Sylvain Brunet, Selva Baltan, Bruce D Trapp
Hereditary spastic paraplegia (HSP) is a neurological syndrome characterized by degeneration of central nervous system (CNS) axons. Mutated HSP proteins include myelin proteolipid protein (PLP) and axon-enriched proteins involved in mitochondrial function, smooth endoplasmic reticulum (SER) structure, and microtubule (MT) stability/function. We characterized axonal mitochondria, SER, and MTs in rodent optic nerves where PLP is replaced by the peripheral nerve myelin protein, P0 (P0-CNS mice). Mitochondrial pathology and degeneration were prominent in juxtaparanodal axoplasm at 1 mo of age...
November 21, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27870323/inflammasome-activators-induce-fibronectin-expression-and-release-in-macrophages
#20
Hye-Kyoung Jun, Young-Jung Jung, Bong-Kyu Choi
Extracellular fibronectin (Fn) can activate pro-inflammatory pathways and serves as an endogenous danger signalling molecule; thus, it has been suggested as a biomarker for several diseases. In the present study, we found that pathogen-derived activators of the inflammasomes induce the expression and secretion of Fn in macrophages through a mechanism involving adenosine triphosphate (ATP) and caspase-1 activation. We also found that plasma Fn induces caspase-1 activation and cell death in macrophages, epithelial cells, and fibroblasts...
November 21, 2016: Cellular Microbiology
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