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cyclic Adenosine monophosphate

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https://www.readbyqxmd.com/read/29223715/development-of-two-fluorine-18-labeled-pet-radioligands-targeting-pde10a-and-in-vivo-pet-evaluation-in-nonhuman-primates
#1
Vladimir Stepanov, Akihiro Takano, Ryuji Nakao, Nahid Amini, Shotaro Miura, Tomoaki Hasui, Haruhide Kimura, Takahiko Taniguchi, Christer Halldin
INTRODUCTION: Phosphodiesterase 10A (PDE10A) is a member of the PDE enzyme family that degrades cyclic adenosine and guanosine monophosphates (cAMP and cGMP). Based on the successful development of [11C]T-773 as PDE10A positron emission tomography (PET) radioligand, in this study our aim was to develop and evaluate fluorine-18 analogs of [11C]T-773. METHODS: [18F]FM-T-773-d2 and [18F]FE-T-773-d4 were synthesized from the same precursor used for 11C-labeling of T-773 in a two-step approach via 18F-fluoromethylation and 18F-fluoroethylation, respectively, using corresponding deuterated synthons...
October 23, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/29214744/exposure-to-cadmium-during-gestation-and-lactation-affects-development-and-function-of-leydig-cells-in-male-offspring
#2
Huajian Tian, Shaomin Chen, Yang Leng, Teng Li, Zengli Li, Hongxia Chen, Qihao Zhang
Toxic effects of maternal exposure to Cadmium (Cd) on Leydig cells of male offspring arises much concern recently, but its toxic effects on the development of Leydig cells and androgen synthesis have not been elucidated. In this study, female rats were exposed to Cd during gestation and lactation, and the development of Leydig cells in the first filial-generation (F1) male rats was investigated. The steroidogenic signaling pathway and biomarkers related to the development of Leydig cells were detected to disclose how maternal Cd-exposure caused reproductive damage...
December 7, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/29210121/proanthocyanidin-rich-pinus-radiata-bark-extract-inhibits-mast-cell-mediated-anaphylaxis-like-reactions
#3
Yun Ho Choi, Chang Ho Song, Sung Phil Mun
Mast cells play a critical role in the effector phase of immediate hypersensitivity and allergic reactions. Pinus radiata bark extract exerts multiple biological effects and exhibits immunomodulatory and antioxidant properties. However, its role in mast cell-mediated anaphylactic reactions has not been thoroughly investigated. In this study, we examined the effects of proanthocyanidin-rich water extract (PAWE) isolated from P. radiata bark on compound 48/80-induced or antidinitrophenyl (DNP) immunoglobulin E (IgE)-mediated anaphylaxis-like reactions in vivo...
December 6, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29204911/repeated-shock-stress-facilitates-basolateral-amygdala-synaptic-plasticity-through-decreased-camp-specific-phosphodiesterase-type-iv-pde4-expression
#4
Steve Ryan, Chenchen Li, Aurélie Menigoz, Rimi Hazra, Joanna Dabrowska, David Ehrlich, Katelyn Gordon, Donald G Rainnie
Previous studies have shown that exposure to stressful events can enhance fear memory and anxiety-like behavior as well as increase synaptic plasticity in the rat basolateral amygdala (BLA). We have evidence that repeated unpredictable shock stress (USS) elicits a long-lasting increase in anxiety-like behavior in rats, but the cellular mechanisms mediating this response remain unclear. Evidence from recent morphological studies suggests that alterations in the dendritic arbor or spine density of BLA principal neurons may underlie stress-induced anxiety behavior...
December 4, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/29203646/structural-and-biochemical-characterization-of-the-catalytic-domains-of-gdpp-reveals-a-unified-hydrolysis-mechanism-for-the-dhh-dhha1-phosphodiesterase
#5
Feng Wang, Qing He, Kaixuan Su, Tiandi Wei, Sujuan Xu, Lichuan Gu
The Asp-His-His and Asp-His-His-associated (DHH/DHHA1) domain-containing phosphodiesterases (PDEs) that catalyze degradation of cyclic di-adenosine monophosphate (c-di-AMP) could be subdivided into two subfamilies based on the final product is 5'-phosphadenylyl-adenosine (5'-pApA) or AMP. In previous study we revealed that Rv2837c, a stand-alone DHH/DHHA1 PDE, employs a 5'-pApA internal flipping mechanism to produce AMPs. However, why the membrane-bound DHH/DHHA1 PDE can only degrade c-di-AMP to 5'-pApA remains obscure...
December 4, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29201000/striatal-g%C3%AE-olf-camp-signal-dependent-mechanism-to-generate-levodopa-induced-dyskinesia-in-parkinson-s-disease
#6
Satoshi Goto
The motor symptoms of Parkinson's disease (PD) result from striatal dopamine (DA) deficiency due to a progressive degeneration of nigral dopaminergic cells. Although DA replacement therapy is the mainstay to treat parkinsonian symptoms, a long-term daily administration of levodopa often develops levodopa-induced dyskinesia (LID). LID is closely linked to the dysregulation of cyclic adenosine monophosphate (cAMP) signaling cascades in the medium spiny neurons (MSNs), the principal neurons of the striatum, which are roughly halved with striatonigral MSNs by striatopallidal MSNs...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29200726/influence-of-flavonoids-on-mechanism-of-modulation-of-insulin-secretion
#7
Juliana Mikaelly Dias Soares, Ana Ediléia Barbosa Pereira Leal, Juliane Cabral Silva, Jackson R G S Almeida, Helinando Pequeno de Oliveira
Background: The development of alternatives for insulin secretion control in vivo or in vitro represents an important aspect to be investigated. In this direction, natural products have been progressively explored with this aim. In particular, flavonoids are potential candidates to act as insulin secretagogue. Objective: To study the influence of flavonoid on overall modulation mechanisms of insulin secretion. Methods: The research was conducted in the following databases and platforms: PubMed, Scopus, ISI Web of Knowledge, SciELO, LILACS, and ScienceDirect, and the MeSH terms used for the search were flavonoids, flavones, islets of Langerhans, and insulin-secreting cells...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29175000/cyclic-nucleotide-signaling-changes-associated-with-normal-aging-and-age-related-diseases-of-the-brain
#8
REVIEW
Michy P Kelly
Deficits in brain function that are associated with aging and age-related diseases benefit very little from currently available therapies, suggesting a better understanding of the underlying molecular mechanisms is needed to develop improved drugs. Here, we review the literature to test the hypothesis that a break down in cyclic nucleotide signaling at the level of synthesis, execution, and/or degradation may contribute to these deficits. A number of findings have been reported in both the human and animal model literature that point to brain region-specific changes in Galphas (a...
November 23, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29162743/akap95-mediated-nuclear-anchoring-of-pka-mediates-cortisol-induced-ptgs2-expression-in-human-amnion-fibroblasts
#9
Jiangwen Lu, Wangsheng Wang, Yabing Mi, Chuyue Zhang, Hao Ying, Luyao Wang, Yawei Wang, Leslie Myatt, Kang Sun
Phosphorylation of the transcription factors cyclic adenosine monophosphate response element-binding protein (CREB) and signal transducer and activator of transcription 3 (STAT3) by protein kinase A (PKA) is required for the cortisol-induced production of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in human amnion fibroblasts, which critically mediates human parturition (labor). We found that PKA was confined in the nucleus by A-kinase-anchoring protein 95 (AKAP95) in amnion fibroblasts and that this localization was key to the cortisol-induced expression of PTGS2, the gene encoding COX-2...
November 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/29162108/reduced-suppressive-effect-of-%C3%AE-2-adrenoceptor-agonist-on-fibrocyte-function-in-severe-asthma
#10
Chun-Yu Lo, Charalambos Michaeloudes, Pankaj K Bhavsar, Chien-Da Huang, Po-Jui Chang, Chun-Hua Wang, Han-Pin Kuo, Kian Fan Chung
BACKGROUND: Patients with severe asthma have increased airway remodelling and elevated numbers of circulating fibrocytes with enhanced myofibroblastic differentiation capacity, despite being treated with high doses of corticosteroids, and long acting β2-adrenergic receptor (AR) agonists (LABAs). We determined the effect of β2-AR agonists, alone or in combination with corticosteroids, on fibrocyte function. METHODS: Non-adherent non-T cells from peripheral blood mononuclear cells isolated from healthy subjects and patients with non-severe or severe asthma were treated with the β2-AR agonist, salmeterol, in the presence or absence of the corticosteroid dexamethasone...
November 21, 2017: Respiratory Research
https://www.readbyqxmd.com/read/29161257/regulation-of-camp-and-gsk3-signaling-pathways-contributes-to-the-neuronal-conversion-of-glioma
#11
Jinsoo Oh, Yongbo Kim, Lihua Che, Jeong Beom Kim, Gyeong Eon Chang, Eunji Cheong, Seok-Gu Kang, Yoon Ha
Glioma is the most malignant type of primary central nervous system tumors, and has an extremely poor prognosis. One potential therapeutic approach is to induce the terminal differentiation of glioma through the forced expression of pro-neural factors. Our goal is to show the proof of concept of the neuronal conversion of C6 glioma through the combined action of small molecules. We investigated the various changes in gene expression, cell-specific marker expression, signaling pathways, physiological characteristics, and morphology in glioma after combination treatment with two small molecules (CHIR99021, a glycogen synthase kinase 3 [GSK3] inhibitor and forskolin, a cyclic adenosine monophosphate [cAMP] activator)...
2017: PloS One
https://www.readbyqxmd.com/read/29159836/mechanisms-of-calcium-sequestration-by-isolated-malpighian-tubules-of-the-house-cricket-acheta-domesticus
#12
Austin Browne, Michael J O'Donnell
Hemolymph calcium homeostasis in insects is achieved by the Malpighian tubules, primarily by sequestering excess Ca(2+) within internal calcium stores (Ca-rich granules) most often located within type I (principal) tubule cells. Using both the scanning ion-selective electrode technique and the Ramsay secretion assay this study provides the first measurements of basolateral and transepithelial Ca(2+) fluxes across the Malpighian tubules of an Orthopteran insect, the house cricket Acheta domesticus. Ca(2+) transport was specific to midtubule segments, where 97% of the Ca(2+) entering the tubule is sequestered within intracellular calcium stores and the remaining 3% is secreted into the lumen...
November 21, 2017: Archives of Insect Biochemistry and Physiology
https://www.readbyqxmd.com/read/29158149/the-role-of-hydrogen-sulfide-in-cyclic-nucleotide-signaling
#13
REVIEW
Xu Cao, Zhiyuan Wu, Siping Xiong, Lei Cao, Gautam Sethi, Jin-Song Bian
Hydrogen sulfide (H2S) is recognized as an endogenous gaseous transmitter alongside nitric oxide (NO) and carbon monoxide (CO). By integrating into multiple signaling pathways, H2S elicits biological functions in various mammalian systems. Among these pathways, cyclic nucleotide signaling has gradually gained attention in the past decade. Based on current evidence, it seems that H2S may differentially affect the activity of resting adenylyl cyclases (ACs) and activated ACs, therefore playing a dual role in the regulation of cyclic adenosine monophosphate (cAMP) mediated signaling...
November 17, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29157895/a-novel-homozygous-mutation-in-the-fshr-gene-is-causative-for-primary-ovarian-insufficiency
#14
Hongli Liu, Xiaofei Xu, Ting Han, Lei Yan, Lei Cheng, Yingying Qin, Wen Liu, Shidou Zhao, Zi-Jiang Chen
OBJECTIVE: To identify the potential FSHR mutation in a Chinese woman with primary ovarian insufficiency (POI). DESIGN: Genetic and functional studies. SETTING: University-based reproductive medicine center. PATIENT(S): A POI patient, her family members, and another 192 control women with regular menstruation. INTERVENTION(S): Ovarian biopsy was performed in the patient. Sanger sequencing was carried out for the patient, her sister, and parents...
November 18, 2017: Fertility and Sterility
https://www.readbyqxmd.com/read/29155580/a-unique-approach-to-design-potent-and-selective-cyclic-adenosine-monophosphate-response-element-binding-protein-binding-protein-cbp-inhibitors
#15
Sarah M Bronner, Jeremy M Murray, F Anthony Romero, Kwong Wah Lai, Vickie Tsui, Patrick Cyr, Maureen H Beresini, Gladys de Leon Boenig, Zhongguo Chen, Edna F Choo, Kevin R Clark, Terry D Crawford, Hariharan Jayaram, Susan Kaufman, Ruina Li, Yingjie Li, Jiangpeng Liao, Xiaorong Liang, Wenfeng Liu, Justin Q Ly, Jonathan Maher, John S Wai, Fei Wang, Aijun Zheng, Xiaoyu Zhu, Steven R Magnuson
The epigenetic regulator CBP/P300 presents a novel therapeutic target for oncology. Previously, we reported the development of potent and selective CBP bromodomain inhibitors by first identifying pharmacophores that bind the KAc region, and then building into the LPF shelf. Herein we report the "hybridization" of a variety of KAc-binding fragments with a tetrahydroquinoline scaffold that makes optimal interactions with the LPF shelf, imparting enhanced potency and selectivity to the hybridized ligand. To demonstrate the utility of our hybridization approach, two analogues containing unique Asn binders and the optimized tetrahydroquinoline moiety were rapidly optimized to yield single-digit nanomolar inhibitors of CBP with exquisite selectivity over BRD4(1) and the broader bromodomain family...
November 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29155261/the-phosphodiesterase-4-inhibitor-fcpr16-attenuates-ischemia-reperfusion-injury-in-rats-subjected-to-middle-cerebral-artery-occlusion-and-reperfusion
#16
Jiajia Chen, Hui Yu, Jiahong Zhong, Hongfang Feng, Haitao Wang, Yufang Cheng, Zhengqiang Zou, Chang Huang, Zhongzhen Zhou, Wenhua Zheng, Jiangping Xu
Current phosphodiesterase-4 (PDE4) inhibitors exert beneficial effects in central nervous system diseases via anti-inflammatory and anti-apoptotic properties, but many of them are plagued by side effects like nausea and emesis. FCPR16, a novel PDE4 inhibitor synthesized in our lab, has potential anti-inflammatory property. In the present study, we aimed to investigate the effects of FCPR16 in a rat model of ischemic stroke and evaluate its emetogenic potential. Our results showed that FCPR16 treatment improved neurological function, reduced cerebral infarct volume, and attenuated brain histological changes in rats subjected to middle cerebral artery occlusion and reperfusion (MCAO/R)...
November 16, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/29152657/dihydroartemisinin-treatment-exhibits-antitumor-effects-in-glioma-cells-through-induction-of-apoptosis
#17
Chun-Hua Xu, Yue Liu, Li-Min Xiao, Chang-Gui Guo, Su-Yue Zheng, Er-Ming Zeng, Dong-Hai Li
The present study aimed to investigate the effect of dihydroartemisinin on the proliferation of chemotherapy‑resistant C6 rat glioma cells. The results revealed that incubation of C6 glioma cells with a range of dihydroartemisinin concentrations for 48 h led to a significant (P<0.02) reduction in the cell number. There was a ‑0.8-fold reduction in the cell count following treatment with 20 µM dihydroartemisinin when compared with the control cultures. Analysis of DNA synthesis using bromodeoxyuridine (BrdU) staining demonstrated a reduction in the BrdU‑labeling index (LI) following treatment with 20 µM dihydroartemisinin...
October 19, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29146813/structural-basis-of-bacterial-transcription-activation
#18
Bin Liu, Chuan Hong, Rick K Huang, Zhiheng Yu, Thomas A Steitz
In bacteria, the activation of gene transcription at many promoters is simple and only involves a single activator. The cyclic adenosine 3',5'-monophosphate receptor protein (CAP), a classic activator, is able to activate transcription independently through two different mechanisms. Understanding the class I mechanism requires an intact transcription activation complex (TAC) structure at a high resolution. Here we report a high-resolution cryo-electron microscopy structure of an intact Escherichia coli class I TAC containing a CAP dimer, a σ70-RNA polymerase (RNAP) holoenzyme, a complete class I CAP-dependent promoter DNA, and a de novo synthesized RNA oligonucleotide...
November 17, 2017: Science
https://www.readbyqxmd.com/read/29146573/prostanoid-ep4-agonist-l-902-688-activates-ppar%C3%AE-and-attenuates-pulmonary-arterial-hypertension
#19
Hsin-Hsien Li, Hsao-Hsun Hsu, Gwo-Jyh Chang, I-Chen Chen, Wan-Jing Ho, Pei-Chen Hsu, Wei-Jan Chen, Jong-Hwei Su Pang, Chung-Chi Huang, Ying-Ju Lai
Prostacyclin agonists that bind the prostacyclin receptor (IP) to stimulate cyclic adenosine monophosphate (cAMP) synthesis are effective vasodilators for the treatment of idiopathic pulmonary arterial hypertension (IPAH) but this signaling may occur through nuclear peroxisome proliferator-activated receptor-gamma (PPARγ). There is evidence of scant IP and PPARγ expression but stable prostanoid EP4 receptor (EP4) expression in IPAH patients. Both IP and EP4 functionally couple with stimulatory G protein (Gs), which activate signal transduction...
November 16, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29146556/shedding-light-on-the-role-of-camp-in-mammalian-sperm-physiology
#20
REVIEW
Melanie Balbach, Vera Beckert, Jan N Hansen, Dagmar Wachten
Mammalian fertilization relies on sperm finding the egg and penetrating the egg vestments. All steps in a sperm's lifetime crucially rely on changes in the second messenger cAMP (cyclic adenosine monophosphate). In recent years, it has become clear that signal transduction in the sperm is not a continuum, but rather organized in subcellular domains, e.g. the sperm head and the sperm flagellum, with the latter being further separated into the midpiece, principal piece,and endpiece. To understand the underlying signaling pathways controlling sperm function in more detail, experimental approaches are needed that allow to study sperm signaling with spatial and temporal precision...
November 13, 2017: Molecular and Cellular Endocrinology
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