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https://www.readbyqxmd.com/read/29148787/acid-base-properties-of-xanthohumol-a-computational-and-experimental-investigation
#1
Marta Arczewska, Daniel M Kamiński, Barbara Gieroba, Mariusz Gagoś
UV-vis spectrophotometry has been applied to determine acid dissociation constants of the prenylated chalcone xanthohumol. The pKa values were compared with those derived from pH-metric titrations. The order of the deprotonation site in the xanthohumol molecule was estimated by quantum mechanical calculations as 2'-OH, 4'-OH, and 4-OH. Furthermore, the electronic and spectroscopic properties of xanthohumol have been investigated on the basis of the time-dependent density functional theory (TDDFT). The TDDFT method, combined with a hybrid exchange-correlation functional using the B3LYP and CAM-B3LYP levels of theory in conjunction with the SMD solvation model, was used to optimize all geometries and predict the excitation energies of the neutral form and ionized species of the chalcone depending on pH value...
November 17, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/29146892/intermedin-ameliorates-atherosclerosis-by-increasing-cholesterol-efflux-through-the-camp-pka-pathway-in-macrophage-raw264-7-cell-line
#2
Hang Liao, Shixi Wan, Xin Zhang, Di Shi, Xiaojiang Zhu, Xiaoping Chen
BACKGROUND The aim of this study was to explore the role of intermedin and its mechanism in cholesterol efflux of macrophage THP-1 and RAW264.7 cell lines in atherosclerosis (AS). MATERIAL AND METHODS ApoE-/- mice were fed with a high-fat diet, and the concentrations of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured. The lipidoses of the aortic sinus were analyzed by hematoxylin and eosin staining, and the cAMP level was detected by enzyme-linked immunosorbent assay (ELISA)...
November 17, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29146573/prostanoid-ep4-agonist-l-902-688-activates-ppar%C3%AE-and-attenuates-pulmonary-arterial-hypertension
#3
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/29146239/innately-activated-tlr4-signal-in-the-nucleus-accumbens-is-sustained-by-crf-amplification-loop-and-regulates-impulsivity
#4
Irina Balan, Kaitlin T Warnock, Adam Puche, Marjorie C Gondre-Lewis, Laure Aurelian
Cognitive impulsivity is a heritable trait believed to represent the behavior that defines the volition to initiate alcohol drinking. We have previously shown that a neuronal Toll-like receptor 4 (TLR4) signal located in the central amygdala (CeA) and ventral tegmental area (VTA) controls the initiation of binge drinking in alcohol-preferring P rats, and TLR4 expression is upregulated by alcohol-induced corticotropin-releasing factor (CRF) at these sites. However, the function of the TLR4 signal in the nucleus accumbens shell (NAc-shell), a site implicated in the control of reward, drug-seeking behavior and impulsivity and the contribution of other signal-associated genes, are still poorly understood...
November 13, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29142472/prostaglandin-e1-protects-hepatocytes-against-endoplasmic-reticulum-stress-induced-apoptosis-via-protein-kinase-a-dependent-induction-of-glucose-regulated-protein-78-expression
#5
Fang-Wan Yang, Yu Fu, Ying Li, Yi-Huai He, Mao-Yuan Mu, Qi-Chuan Liu, Jun Long, Shi-De Lin
AIM: To investigate the protective effect of prostaglandin E1 (PGE1) against endoplasmic reticulum (ER) stress-induced hepatocyte apoptosis, and to explore its underlying mechanisms. METHODS: Thapsigargin (TG) was used to induce ER stress in the human hepatic cell line L02 and hepatocarcinoma-derived cell line HepG2. To evaluate the effects of PGE1 on TG-induced apoptosis, PGE1 was used an hour prior to TG treatment. Activation of unfolded protein response signaling pathways were detected by western blotting and quantitative real-time RT-PCR...
October 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29142291/resveratrol-modulates-cocaine-induced-inhibitory-synaptic-plasticity-in-vta-dopamine-neurons-by-inhibiting-phosphodiesterases-pdes
#6
Yan Li, Laikang Yu, Li Zhao, Fanxing Zeng, Qing-Song Liu
Resveratrol is a natural phytoalexin synthesized by plants, including grapes. It displays a wide range of neuroprotective benefits associated with anti-aging. Recent studies have shown that resveratrol regulates dopaminergic transmission and behavioral effects of drugs of abuse. The goal of the present study is to investigate whether and how resveratrol alters basal inhibitory synaptic transmission and cocaine-induced inhibitory synaptic plasticity in dopamine neurons of the ventral tegmental area (VTA). We report that resveratrol elevated cAMP levels by itself and further potentiated a forskolin-induced increase in cAMP levels in midbrain slices, consistent with reported effects of inhibition of phosphodiesterases (PDEs)...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29140585/timap-the-versatile-protein-phosphatase-1-regulator-in-endothelial-cells
#7
REVIEW
Anita Boratkó, Csilla Csortos
Transforming growth factor (TGF)-β inhibited membrane associated protein, TIMAP, is the member of the myosin phosphatase targeting protein (MYPT) family of protein phosphatase 1 (PP1) regulatory subunits. The N-terminal part of TIMAP has a typical MYPT family structure with a sequence element called MyPhone (myosin phosphatase N-terminal element), a putative bipartite nuclear localization signal, a PP1 catalytic subunit binding motif, and five ankyrin repeats. The C-terminal half of TIMAP is intrinsically disordered, but ends with a functional CAAX box for lipid modification which allows localization of TIMAP at the plasma membrane...
November 15, 2017: IUBMB Life
https://www.readbyqxmd.com/read/29140564/%C3%AE-catenin-and-il-1%C3%AE-dependent-cxcl10-production-drives-progression-of-disease-in-a-mouse-model-of-congenital-hepatic-fibrosis
#8
Eleanna Kaffe, Romina Fiorotto, Francesca Pellegrino, Valeria Mariotti, Mariangela Amenduni, Massimiliano Cadamuro, Luca Fabris, Mario Strazzabosco, Carlo Spirli
Congenital Hepatic Fibrosis (CHF), a genetic disease caused by mutations in the PKHD1 gene, encoding for the protein fibrocystin (FPC), is characterized by biliary dysgenesis, progressive portal fibrosis, and by a PKA-mediated activating phosphorylation of β-Catenin at Ser675. Biliary structures of Pkhd1(del4/del4) mice, a mouse model of CHF, secrete CXCL10 a chemokine able to recruit macrophages. The aim of this study is to clarify whether CXCL10 plays a pathogenetic role in disease progression in CHF/CD and to understand the mechanisms leading to increased CXCL10 secretion...
November 15, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29140280/trpv3-channel-in-keratinocytes-in-scars-with-post-burn-pruritus
#9
Chun Wook Park, Hyun Ji Kim, Yong Won Choi, Bo Young Chung, So-Youn Woo, Dong-Keun Song, Hye One Kim
Post-burn pruritus is a common and distressing sequela of burn scars. Empirical antipruritic treatments usually fail to have a satisfactory outcome because of their limited selectivity and possible side effects. Therefore, novel drug targets need to be identified. Here, we aimed to investigate the possible role of protease-activated receptor 2 (PAR2) and transient receptor potential vanniloid 3 (TRPV3), along with the relation of TRPV3 to thymic stromal lymphopoietin (TSLP). Specimens from normal (unscarred) or burn-scarred (with or without pruritus) tissue were obtained from burn patients for this study...
November 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29138698/soluble-epoxide-hydrolase-inhibitor-and-14-15-epoxyeicosatrienoic-acid-facilitated-long-term-potentiation-through-camp-and-camkii-in-the-hippocampus
#10
Han-Fang Wu, Yi-Ju Chen, Su-Zhen Wu, Chi-Wei Lee, I-Tuan Chen, Yi-Chao Lee, Chi-Chen Huang, Chung-Hsi Hsing, Chih-Wei Tang, Hui-Ching Lin
Epoxyeicosatrienoic acids (EETs) are derived from arachidonic acid and metabolized by soluble epoxide hydrolase (sEH). The role of EETs in synaptic function in the central nervous system is still largely unknown. We found that pharmacological inhibition of sEH to stabilize endogenous EETs and exogenous 14,15-EET significantly increased the field excitatory postsynaptic potential (fEPSP) response in the CA1 area of the hippocampus, while additionally enhancing high-frequency stimulation- (HFS-) induced long-term potentiation (LTP) and forskolin- (FSK-) induced LTP...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/29138065/comparison-of-lipid-dependent-bilayer-insertion-of-phlip-and-its-p20g-variant
#11
Victor Vasquez-Montes, Janessa Gerhart, Kelly E King, Damien Thévenin, Alexey S Ladokhin
The ability of the pH-Low Insertion Peptide (pHLIP) to insert into lipid membranes in a transbilayer conformation makes it an important tool for targeting acidic diseased tissues. pHLIP can also serve as a model template for thermodynamic studies of membrane insertion. We use intrinsic fluorescence and circular dichroism spectroscopy to examine the effect of replacing pHLIP's central proline on the pH-triggered lipid-dependent conformational switching of the peptide. We find that the P20G variant (pHLIP-P20G) has a higher helical propensity than the native pHLIP (pHLIP-WT), in both water:organic solvent mixtures and in the presence of lipid bilayers...
November 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29137290/expression-of-protein-kinase-a-and-the-kappa-opioid-receptor-in-selected-brain-regions-and-conditioned-place-aversion-in-morphine-dependent-rats
#12
Xiuhua Song, Wenqiang Li, Yuzhong Shi, Jingdan Zhang, Yi Li
This study examined adaptive changes in protein kinase A (PKA) and kappa opioid receptor (KOR) in selected addiction-related brain regions before and after conditioned place aversion (CPA). Seventy-two male SD rats were randomly assigned to an experimental group (morphine + naloxone, "MN") and 2 control groups: MS (morphine + saline) and SN (saline + naloxone). MN rats were intraperitoneally injected with morphine twice per day for 6.5 days and naloxone once and trained to establish CPA model. MS and SN rats were injected with equivalent volumes of morphine plus saline and saline plus naloxone, respectively...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136773/the-potential-use-of-melatonin-to-treat-protozoan-parasitic-infections-a-review
#13
REVIEW
Ahmad Daryani, Mahbobeh Montazeri, Abdol Satar Pagheh, Mehdi Sharif, Shahabeddin Sarvi, Azam Hosseinzadeh, Russel J Reiter, Ramtin Hadighi, Mohammad Taghi Joghataei, Habib Ghaznavi, Saeed Mehrzadi
Melatonin (N-acetyl-5-methoxytryptamine) is a circadian hormone produced in vertebrates by the pineal gland and other organs. Melatonin is believed to influence immune cells leading to modulation of the proliferative response of stimulated lymphocytes as well as cytokine production. Due to the antioxidant and immunomodulatory effects of melatonin, it is suggested that this molecule could be a therapeutic alternative agent to fight bacterial, viral, and parasitic infections by a variety of mechanisms. Herein, we review the effects of melatonin on the cell biology of protozoan parasites and host's immune response...
November 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29135990/curcumin-affects-gene-expression-and-reactive-oxygen-species-via-a-pka-dependent-mechanism-in-dictyostelium-discoideum
#14
William S Swatson, Mariko Katoh-Kurasawa, Gad Shaulsky, Stephen Alexander
Botanicals are widely used as dietary supplements and for the prevention and treatment of disease. Despite a long history of use, there is generally little evidence supporting the efficacy and safety of these preparations. Curcumin has been used to treat a myriad of human diseases and is widely advertised and marketed for its ability to improve health, but there is no clear understanding how curcumin interacts with cells and affects cell physiology. D. discoideum is a simple eukaryotic lead system that allows both tractable genetic and biochemical studies...
2017: PloS One
https://www.readbyqxmd.com/read/29133387/insights-into-functions-of-the-h-channel-of-cytochrome-c-oxidase-from-atomistic-molecular-dynamics-simulations
#15
Vivek Sharma, Pablo G Jambrina, Markus Kaukonen, Edina Rosta, Peter R Rich
Proton pumping A-type cytochrome c oxidase (CcO) terminates the respiratory chains of mitochondria and many bacteria. Three possible proton transfer pathways (D, K, and H channels) have been identified based on structural, functional, and mutational data. Whereas the D channel provides the route for all pumped protons in bacterial A-type CcOs, studies of bovine mitochondrial CcO have led to suggestions that its H channel instead provides this route. Here, we have studied H-channel function by performing atomistic molecular dynamics simulations on the entire, as well as core, structure of bovine CcO in a lipid-solvent environment...
November 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29133122/involvement-of-cannabinoid-receptor-type-2-in-light-induced-degeneration-of-cells-from-mouse-retinal-cell-line-in-vitro-and-mouse-photoreceptors-in-vivo
#16
Tomoyo Imamura, Kazuhiro Tsuruma, Yuki Inoue, Tomohiro Otsuka, Yuta Ohno, Shiho Ogami, Shinsaku Yamane, Masamitsu Shimazawa, Hideaki Hara
Earlier studies showed that the expressions of the agonists of the cannabinoid receptors are reduced in the vitreous humor of patients with age-related macular degeneration (AMD), and the cannabinoid type 2 receptor is present in the retinas of rats and monkeys. The purpose of this study was to determine whether the cannabinoid type 2 receptor is involved in the light-induced death of cultured 661W cells, an immortalized murine retinal cell line, and in the light-induced retinal degeneration in mice. Time-dependent changes in the expression and location of retinal cannabinoid type 2 receptor were determined by Western blot and immunostaining...
November 10, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/29131621/expanding-the-armory-predicting-and-tuning-covalent-warhead-reactivity
#17
Richard Lonsdale, Jonathan Burgess, Nicola Colclough, Nichola L Davies, Eva M Lenz, Alexandra Orton, Richard A Ward
Targeted covalent inhibition is an established approach for increasing the potency and selectivity of potential drug candidates, as well as identifying potent and selective tool compounds for target validation studies. It is evident that identification of reversible recognition elements is essential for selective covalent inhibition, but this must also be achieved with the appropriate level of inherent reactivity of the reactive functionality (or 'warhead'). Structural changes that increase or decrease warhead reactivity, guided by methods to predict the effect of those changes, have the potential to tune warhead reactivity and negate issues related to potency and/or toxicity...
November 13, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29131613/proton-coupled-electron-transfer-and-substituent-effects-in-catechol-based-deep-eutectic-solvents-gross-and-fine-tuning-of-redox-activity
#18
Parker J Smith, John C Goeltz
The 1,2-diol moiety in a variety of substituted catechols allows formation of room temperature ionic melts in a 2:1 ratio with choline chloride or choline dihydrogen citrate. These deep eutectic solvents were 4.3-6.6 M in redox active catechols. Substituents on 3- and 4-substituted catechols shift both E° and pKa such that Hammett parameters predict the observed Ep for oxidation in square wave voltammetry. The proton acceptor for the proton-coupled oxidation shifts the observed Ep more strongly than the substituents within the substituents and acceptors reported here...
November 13, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29130684/influence-of-proton-acceptors-on-the-proton-coupled-electron-transfer-reaction-kinetics-of-a-ruthenium-tyrosine-complex
#19
J Christian Lennox, Jillian L Dempsey
A polypyridyl ruthenium complex with fluorinated bipyridine ligands and a covalently bound tyrosine moiety was synthesized, and its photo-induced proton-coupled electron transfer (PCET) reactivity in acetonitrile was investigated with transient absorption spectroscopy. Using flash-quench methodology with methyl viologen as an oxidative quencher, a Ru(3+) species is generated that is capable of initiating the intramolecular PCET oxidation of the tyrosine moiety. Using a series of substituted pyridine bases, the reaction kinetics were found to vary as a function of proton acceptor concentration and identity, with no significant H/D kinetic isotope effect...
November 13, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29128805/ursolic-acid-affords-antidepressant-like-effects-in-mice-through-the-activation-of-pka-pkc-camk-ii-and-mek1-2
#20
Ana B Ramos-Hryb, Mauricio P Cunha, Francis L Pazini, Vicente Lieberknecht, Rui D S Prediger, Manuella P Kaster, Ana Lúcia S Rodrigues
BACKGROUND: Ursolic acid has been shown to display antidepressant-like effects in mice through the modulation of monoaminergic systems. In this study, we sought to investigate the involvement of signaling pathways on the antidepressant-like effects of ursolic acid. METHODS: Mice were treated orally with ursolic acid (0.1mg/kg) and, 45min later they received the followings inhibitors by intracerebroventricular route: H-89 (PKA inhibitor, 1μg/mouse), KN-62 (CAMK-II inhibitor, 1μg/mouse), chelerythrine (PKC inhibitor, 1μg/mouse), U0126 (MEK1/2 inhibitor, 5μg/mouse), PD98059 (MEK1/2 inhibitor, 5μg/mouse), wortmannin (PI3K irreversible inhibitor, 0...
May 24, 2017: Pharmacological Reports: PR
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