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https://www.readbyqxmd.com/read/28625489/diosmin-reduces-chronic-constriction-injury-induced-neuropathic-pain-in-mice
#1
Mariana M Bertozzi, Ana C Rossaneis, Victor Fattori, Daniela T Longhi-Balbinot, Andressa Freitas, Fernando Q Cunha, José C Alves-Filho, Thiago M Cunha, Rubia Casagrande, Waldiceu A Verri
Injury or dysfunction of somatosensory system induces a complex syndrome called neuropathic pain, which still needs adequate pharmacological control. The current pharmacological treatments were in part developed from natural compounds. Flavonoids are natural polyphenolic molecules presenting varied biological activities and low toxicity. The flavonoid diosmin is a safe compound with good tolerability and low toxicity. This study evaluated the antinociceptive effect of diosmin in the sciatic nerve chronic constriction injury (CCI)-induced neuropathic pain model...
June 15, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28624955/presynaptic-inhibition-of-nociceptive-neurotransmission-by-somatosensory-neuron-secreted-suppressors
#2
REVIEW
Kaicheng Li, Bing Cai, Changlin Li, Xu Zhang
Noxious stimuli cause pain by activating cutaneous nociceptors. The Aδ- and C-fibers of dorsal root ganglion (DRG) neurons convey the nociceptive signals to the laminae I-II of spinal cord. In the dorsal horn of spinal cord, the excitatory afferent synaptic transmission is regulated by the inhibitory neurotransmitter γ-aminobutyric acid and modulators such as opioid peptides released from the spinal interneurons, and by serotonin, norepinepherine and dopamine from the descending inhibitory system. In contrast to the accumulated evidence for these central inhibitors and their neural circuits in the dorsal spinal cord, the knowledge about the endogenous suppressive mechanisms in nociceptive DRG neurons remains very limited...
June 15, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28614771/mantidis-ootheca-induces-vascular-relaxation-through-pi3k-akt-mediated-nitric-oxide-cyclic-gmp-protein-kinase-g-signaling-in-endothelial-cells
#3
H Y Kim, Y J Lee, B H Han, J J Yoon, Y M Ahn, M H Hong, R Tan, D G Kang, H S Lee
Mantidis ootheca (Sang Piao Xiao) is well known mantis eggs in a foamy pouch. The purpose of the present study was to investigate the underlying cellular mechanisms of the nitric oxide (NO)-releasing property of the aqueous extract of Mantidis ootheca (AMO) in rat aorta and vascular endothelial cells. AMO was examined for its vascular relaxant effect in isolated phenylephrine-precontracted rat thoracic aortic rings. The roles of the nitric oxide (NO) signaling in the AMO-induced effects were tested in human umbilical vein endothelial cells (HUVECs)...
April 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28592587/linaclotide-activates-guanylate-cyclase-c-cgmp-protein-kinase-ii-dependent-trafficking-of-cftr-in-the-intestine
#4
Md Kaimul Ahsan, Boris Tchernychev, Marco M Kessler, Robert M Solinga, David Arthur, Cristina I Linde, Inmaculada Silos-Santiago, Gerhard Hannig, Nadia A Ameen
The transmembrane receptor guanylyl cyclase-C (GC-C), expressed on enterocytes along the intestine, is the molecular target of the GC-C agonist peptide linaclotide, an FDA-approved drug for treatment of adult patients with Irritable Bowel Syndrome with Constipation and Chronic Idiopathic Constipation. Polarized human colonic intestinal cells (T84, CaCo-2BBe) rat and human intestinal tissues were employed to examine cellular signaling and cystic fibrosis transmembrane conductance regulator (CFTR)-trafficking pathways activated by linaclotide using confocal microscopy, in vivo surface biotinylation, and protein kinase-II (PKG-II) activity assays...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28591657/agc-kinases-mechanisms-of-regulation-%C3%A2-and-innovative-drug-development
#5
REVIEW
Alejandro E Leroux, Jörg Schulze, Ricardo M Biondi
The group of AGC kinases consists of 63 evolutionarily related serine/threonine protein kinases comprising PDK1, PKB/Akt, SGK, PKC, PRK/PKN, MSK, RSK, S6K, PKA, PKG, DMPK, MRCK, ROCK, NDR, LATS, CRIK, MAST, GRK, Sgk494, and YANK, while two other families, Aurora and PLK, are the most closely related to the group. Eight of these families are physiologically activated downstream of growth factor signaling, while other AGC kinases are downstream effectors of a wide range of signals. The different AGC kinase families share aspects of their mechanisms of inhibition and activation...
June 4, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28585197/human-protein-kinases-and-obesity
#6
Atilla Engin
The action of protein kinases and protein phosphatases is essential for multiple physiological responses. Each protein kinase displays its own unique substrate specificity, and a regulatory mechanism that may be modulated by association with other proteins. Protein kinases are classified by the target amino acid in their substrates. Some protein kinases can phosphorylate both serine/threonine, as well as tyrosine residues. This group of kinases has been known as dual specificity kinases. Unlike the dual specificity kinases, a heterogeneous group of protein phosphatases are known as dual-specificity phosphatases...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28584062/cytochrome-b5-reductase-3-modulates-soluble-guanylate-cyclase-redox-state-and-cgmp-signaling
#7
Mizanur M Rahaman, Anh T Nguyen, Megan P Miller, Scott A Hahn, Courtney Sparacino-Watkins, Soma Jobbagy, Nolan T Carew, Nadiezhda Cantu-Medellin, Katherine C Wood, Catherine Baty, Francisco J Schopfer, Eric E Kelley, Mark T Gladwin, Emil Martin, Adam C Straub
Rationale: Soluble guanylate cyclase (sGC) heme iron, in its oxidized state (Fe(3+)), is desensitized to nitric oxide (NO) and limits cyclic guanosine 3', 5'-monophosphate (cGMP) production needed for downstream activation of PKG-dependent signaling and blood vessel dilation. Objective: While reactive oxygen species are known to oxidize the sGC heme iron, the basic mechanism(s) governing sGC heme iron recycling to its NO-sensitive, reduced state, remain poorly understood. Methods and Results: Oxidant challenge studies show vascular smooth muscle cells have an intrinsic ability to reduce oxidized sGC heme iron and form protein-protein complexes between cytochrome b5 reductase 3 (Cyb5R3), also known as methemoglobin reductase, and oxidized sGC...
June 5, 2017: Circulation Research
https://www.readbyqxmd.com/read/28583991/mutations-of-pka-cyclic-nucleotide-binding-domains-reveal-novel-aspects-of-cyclic-nucleotide-selectivity
#8
Robin Lorenz, Eui-Whan Moon, Jeong Joo Kim, Sven H Schmidt, Banumathi Sankaran, Ioannis V Pavlidis, Choel Kim, Friedrich W Herberg
Cyclic AMP and cyclic GMP are ubiquitous second messengers that regulate the activity of effector proteins in all forms of life. The main effector proteins, the cAMP-dependent protein kinase (PKA) and the cGMP-dependent protein kinase (PKG), are preferentially activated by cAMP and cGMP, respectively. However, the molecular basis of this cyclic nucleotide is still not fully understood. Analysis of isolated cyclic nucleotide binding (CNB) domains of PKA RIα reveals that the C-terminal CNB-B has a higher cAMP affinity and selectivity than the N-terminal CNB-A...
June 5, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28580416/glua2-lacking-ampa-receptors-and-nitric-oxide-signaling-gate-spike-timing-dependent-potentiation-of-glutamate-synapses-in-the-dorsal-raphe-nucleus
#9
Samir Haj-Dahmane, Jean Claude Béïque, Roh-Yu Shen
The dorsal raphe nucleus (DRn) receives glutamatergic inputs from numerous brain areas that control the function of DRn serotonin (5-HT) neurons. By integrating these synaptic inputs, 5-HT neurons modulate a plethora of behaviors and physiological functions. However, it remains unknown whether the excitatory inputs onto DRn 5-HT neurons can undergo activity-dependent change of strength, as well as the mechanisms that control their plasticity. Here, we describe a novel form of spike-timing-dependent long-term potentiation (tLTP) of glutamate synapses onto rat DRn 5-HT neurons...
May 2017: ENeuro
https://www.readbyqxmd.com/read/28579171/the-ndr-lats-protein-kinases-in-immunology-and-cancer-biology
#10
REVIEW
Ahmad A D Sharif, Alexander Hergovich
The NDR (nuclear Dbf2-related)/LATS (large tumour suppressor) family of kinases represents a subclass of the AGC (protein kinase A (PKA)/PKG/PKC-like) group of serine/threonine protein kinases. Members of the NDR/LATS family are vital components of conserved pathways controlling essential cellular processes, such as proliferation (cell cycle progression) and cell death. In particular, the central involvement of NDR/LATS as YAP/TAZ kinases in the Hippo tissue growth control pathway has gained much interest. In this review, we summarize the roles of mammalian NDR1/2 (aka STK38/STK38L) and LATS1/2 in immunity and cancer biology...
June 1, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28578165/antihypertensive-and-vasorelaxant-effects-of-aqueous-extract-of-artemisia-campestris-l-from-eastern-morocco
#11
Ikram Dib, Monique Tits, Luc Angenot, Jean Noel Wauters, Asmae Assaidi, Hassane Mekhfi, Mohammed Aziz, Mohammed Bnouham, Abdelkhaleq Legssyer, Michel Frederich, Abderrahim Ziyyat
ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia campestris L. (Asteraceae) has many traditional uses, among which treatment of diabetes and hypertension. AIM OF THE STUDY: This study was conducted in order to confirm the antihypertensive and hypotensive effects of A. campestris L. aqueous extract (AcAE) and to explore the underlying mechanism of action of its vasorelaxant effect, besides the acute toxicity. Also, the chemical composition of AcAE was investigated. MATERIAL AND METHODS: the chemical content of AcAE was determined by using HPLC and NMR techniques...
May 31, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28571764/protein-kinase-c-pkc-isoforms-in-cancer-tumor-promotion-and-tumor-suppression
#12
REVIEW
Noah Isakov
The AGC family of serine/threonine kinases (PKA, PKG, PKC) includes more than 60 members that are critical regulators of numerous cellular functions, including cell cycle and differentiation, morphogenesis, and cell survival and death. Mutation and/or dysregulation of AGC kinases can lead to malignant cell transformation and contribute to the pathogenesis of many human diseases. Members of one subgroup of AGC kinases, the protein kinase C (PKC), have been singled out as critical players in carcinogenesis, following their identification as the intracellular receptors of phorbol esters, which exhibit tumor-promoting activities...
May 29, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28559397/cyclic-nucleotides-differentially-regulate-cx43-gap-junction-function-in-uterine-artery-endothelial-cells-from-pregnant-ewes
#13
Bryan C Ampey, Amanda C Ampey, Gladys E Lopez, Ian M Bird, Ronald R Magness
Cell-cell communication is dependent on GJ (gap junction) proteins such as Cx43 (connexin 43). We previously demonstrated the importance of Cx43 function in establishing the enhanced pregnancy vasodilatory phenotype during pregnancy in uterine artery endothelial cells from pregnant (P-UAEC) ewes. Cx43 is regulated by elevating cAMP and PKA (protein kinase A)-dependent Cx43 S365 phosphorylation-associated trafficking and GJ open gating, which is opposed by PKC (protein kinase C)-dependent S368 phosphorylation-mediated GJ turnover and closed gating...
May 30, 2017: Hypertension
https://www.readbyqxmd.com/read/28550175/chronic-hypoxia-attenuates-the-vasodilator-efficacy-of-protein-kinase-g-in-fetal-and-adult-ovine-cerebral-arteries
#14
Richard B Thorpe, Margaret C Hubbell, Jinjutha Silpanisong, James M Williams, William J Pearce
Long-term hypoxia (LTH) attenuates nitric oxide (NO) induced vasorelaxation in ovine middle cerebral arteries. Because cGMP-dependent protein kinase (PKG) is an important mediator of NO signaling in vascular smooth muscle, we tested the hypothesis that LTH diminishes the ability of PKG to interact with target proteins and cause vasorelaxation. Prominent among proteins that regulate vascular tone is the large conductance calcium-sensitive potassium (BK) channel, which is a substrate for PKG and is responsive to phosphorylation on multiple serine/threonine residues...
May 26, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28550173/experimental-cardiac-radiation-exposure-induces-ventricular-diastolic-dysfunction-with-preserved-ejection-fraction
#15
Hirofumi Saiki, Gilles Moulay, Adam J Guenzel, Weibin Liu, Teresa Decklever, Kelly Classic, Linh Pham, Horng H Chen, John C Burnett, Stephen J Russell, Margaret M Redfield
BACKGROUND: Breast cancer radiotherapy increases the risk of heart failure (HF) with preserved ejection fraction (HFpEF). Cardiomyocytes are highly radio-resistant but radiation specifically affects coronary microvascular endothelial cells with subsequent microvascular inflammation and rarefaction. The effects of radiation on left ventricular (LV) diastolic function are poorly characterized. We hypothesized that cardiac radiation exposure may result in diastolic dysfunction without reduced EF...
May 26, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28546515/the-interaction-between-the-wnt-%C3%AE-catenin-signaling-cascade-and-pkg-activation-in-cancer
#16
Kevin Lee, Gary A Piazza
The activation of the Wnt/β-catenin signaling cascade has been well studied and documented in colorectal cancer (CRC). The long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) has been shown to reduce the incidence and risk of death from CRC in numerous epidemiological studies. The NSAID sulindac has also been reported to cause regression of precancerous adenomas in individuals with familial adenomatous polyposis who are at high risk of developing CRC. The mechanism responsible for cancer chemopreventive activity of NSAIDs is not well understood but may be unrelated to their cyclooxygenase inhibitory activity...
April 6, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28526706/cardiac-hyporesponsiveness-in-severe-sepsis-is-associated-with-nitric-oxide-dependent-activation-of-g-protein-receptor-kinase
#17
Daniela Dal-Secco, Silvia DalBó, Natalia E S Lautherbach, Fábio N Gava, Mara Rubia Nunes Celes, Patricia Oliveira Benedet, Adriana H Souza, Juliana Akinaga, Vanessa Lima, Katiussia P Silva, Luiz Ricardo A Kiguti, Marcos A Rossi, Isis do Carmo Kettelhut, André Sampaio Pupo, Fernando Queiroz Cunha, Jamil Assreuy
G protein-coupled receptor kinase isoform 2 (GRK2) has a critical role in physiological and pharmacological responses to endogenous and exogenous substances. Sepsis causes an important cardiovascular dysfunction in which nitric oxide (NO) has a relevant role. The present study aimed to assess the putative effect of inducible NO synthase (NOS-2)-derived NO on the activity of GRK2 in the context of septic cardiac dysfunction. C57BL/6 mice were submitted to severe septic injury by cecal ligation and puncture (CLP)...
May 19, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28515175/role-for-reactive-oxygen-species-in-flow-stimulated-inner-medullary-collecting-duct-endothelin-1-production
#18
Will Wheatley, Donald E Kohan
Inner medullary collecting duct (IMCD)-derived endothelin-1 (ET-1) is stimulated by volume expansion, in part through augmented luminal flow, whereupon it can elicit natriuresis and diuresis. Since flow can alter nitric oxide (NO) and reactive oxygen species (ROS), both of which can affect collecting duct salt transport, we asked whether NO and/or ROS mediate flow-stimulated IMCD ET-1. Mouse IMCD3 cells were exposed to flow and ET-1/GAPDH mRNA assessed. A shear stress of 10 dyne/cm2 for 1 hr increased ET-1 mRNA by 4-fold compared to no flow (ET-1 flow response)...
May 17, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28509344/cgmp-signalling-inhibits-platelet-shape-change-through-regulation-of-the-rhoa-rho-kinase-mlc-phosphatase-signalling-pathway
#19
Ahmed Aburima, Kochar Walladbegi, Jonathan D Wake, Khalid M Naseem
BACKGROUND: Platelet shape change, spreading and thrombus stability requires activation of the actin cytoskeleton contractile machinery. The mechanisms controlling actin assembly to prevent unwanted platelet activation are unclear. OBJECTIVES: We examined the effects of nitric oxide on the signalling pathways regulating platelet actin-myosin activation. RESULTS: S-nitrosoglutathione (GSNO) inhibited thrombin-induced platelet shape change and myosin phosphorylation of myosin light chain (MLC)...
May 16, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28506928/distinct-phosphodiesterase-5a-containing-compartments-allow-selective-regulation-of-cgmp-dependent-signalling-in-human-arterial-smooth-muscle-cells
#20
Lindsay S Wilson, Manhong Guo, M Bibiana Umana, Donald H Maurice
Cyclic GMP (cGMP) translates and integrates much of the information encoded by nitric oxide (NO(·)) and several natriuretic peptides, including the atrial natriuretic peptide (ANP). Previously, we reported that integration of a cGMP-specific cyclic nucleotide phosphodiesterase, namely phosphodiesterase 5A (PDE5A), into a protein kinase G (PKG)- and inositol-1,4,5-trisphosphate receptor (IP3R)-containing endoplasmic reticulum (ER) signalosome allows localized control of PDE5A activity and of PKG-dependent inhibition of IP3-mediated release of ER Ca(2+) in human platelets...
May 12, 2017: Cellular Signalling
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