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https://www.readbyqxmd.com/read/28405672/glucagon-like-peptide-1-related-peptides-increase-nitric-oxide-effects-to-reduce-platelet-activation
#1
Cristina Barale, Simona Buracco, Franco Cavalot, Chiara Frascaroli, Angelo Guerrasio, Isabella Russo
Glucagon-like peptide 1 (GLP-1) is object of intensive investigation for not only its metabolic effects but also the protective vascular actions. Since platelets exert a primary role in the pathogenesis of atherosclerosis, inflammation and vascular complications, we investigated whether GLP-1 directly influences platelet reactivity. For this purpose, in platelets from 72 healthy volunteers we evaluated GLP-1 receptor (GLP-1R) expression and the effects of a 15-minute incubation with the native form GLP-1(7-36), the N-terminally truncated form GLP-1(9-36) and the GLP-1 analogue Liraglutide (100 nmol/l) on: i) aggregation induced by collagen or arachidonic acid (AA); ii) platelet function under shear stress; iii) cGMP and cAMP synthesis and cGMP-dependent protein kinase (PKG)-induced Vasodilator-Stimulated-Phosphoprotein (VASP) phosphorylation; iv) activation of the signalling molecules Phosphatidylinositol 3-Kinase (PI3-K)/Akt and Mitogen Activated Protein Kinase (MAPK)/ERK-1/2; and v) oxidative stress...
April 13, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28404873/sulfhydration-associated-phosphodiesterase-5a-dimerization-mediates-vasorelaxant-effect-of-hydrogen-sulfide
#2
Yan Sun, Yaqian Huang, Wen Yu, Siyao Chen, Qiuyu Yao, Chunyu Zhang, Dingfang Bu, Chaoshu Tang, Junbao Du, Hongfang Jin
The study was designed to examine if the vasorelaxant effect of hydrogen sulfide was mediated by sulfhydration-associated phosphodiesterase (PDE) 5A dimerization. The thoracic aorta of rat was separated and the vasorelaxant effects were examined with in vitro vascular perfusion experiments. The dimerization and sulfhydration of PDE 5A and soluble guanylatecyclase (sGC) were measured. PDE 5A and protein kinase G (PKG) activities were tested. Intracellular cGMP content was detected by enzyme-linked immunosorbent assay (ELISA)...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28376489/triiodothyronine-potentiates-vasorelaxation-via-pkg-vasp-signaling-in-vascular-smooth-muscle-cells
#3
Sherin Samuel, Kuo Zhang, Yi-Da Tang, A Martin Gerdes, Maria Alicia Carrillo-Sepulveda
BACKGROUND/AIMS: Vascular relaxation caused by Triiodothyronine (T3) involves direct activation of endothelial cells (EC) and vascular smooth muscle cells (VSMC). Activation of protein kinase G (PKG) has risen as a novel contributor to the vasorelaxation mechanism triggered by numerous stimuli. We hypothesize that T3-induced vasorelaxation involves PKG/vasodilator-stimulated phosphoprotein (VASP) signaling pathway in VSMC. METHODS: Human aortic endothelial cells (HAEC) and VSMC were treated with T3 for short (2 to 60 minutes) and long term (24 hours)...
April 4, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28365422/mechanisms-of-the-cyclic-nucleotide-cross-talk-signaling-network-in-cardiac-l-type-calcium-channel-regulation
#4
Claire Y Zhao, Joseph L Greenstein, Raimond L Winslow
Regulation of L-type Calcium (Ca(2+)) Channel (LCC) gating is critical to shaping the cardiac action potential (AP) and triggering the initiation of excitation-contraction (EC) coupling in cardiac myocytes. The cyclic nucleotide (cN) cross-talk signaling network, which encompasses the β-adrenergic and the Nitric Oxide (NO)/cGMP/Protein Kinase G (PKG) pathways and their interaction (cross-talk) through distinctively-regulated phosphodiesterase isoenzymes (PDEs), regulates LCC current via Protein Kinase A- (PKA) and PKG-mediated phosphorylation...
March 29, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28358309/zerumbone-alleviates-neuropathic-pain-through-the-involvement-of-l-arginine-nitric-oxide-cgmp-k%C3%A2-%C2%BA-atp-channel-pathways-in-chronic-constriction-injury-in-mice-model
#5
Nurul Atiqah Zulazmi, Banulata Gopalsamy, Jasmine Chia Siew Min, Ahmad Akira Omar Farouk, Mohd Roslan Sulaiman, B Hemabarathy Bharatham, Enoch Kumar Perimal
The present study investigates the involvement of the l-arginine-Nitric Oxide-cGMP-K⁺ ATP pathways responsible for the action of anti-allodynic and antihyperalgesic activities of zerumbone in chronic constriction injury (CCI) induced neuropathic pain in mice. The role of l-arginine-NO-cGMP-K⁺ was assessed by the von Frey and the Randall-Selitto tests. Both allodynia and hyperalgesia assessments were carried out on the 14th day post CCI, 30 min after treatments were given for each respective pathway. Anti-allodynic and antihyperalgesic effects of zerumbone (10 mg/kg, i...
March 30, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28303054/genetic-variability-for-iron-and-zinc-as-well-as-antinutrients-affecting-bioavailability-in-black-gram-vigna-mungo-l-hepper
#6
Jagdish Singh, Rajani Kanaujia, A K Srivastava, G P Dixit, N P Singh
The mineral content of pulses is generally high, but the bioavailability is poor due to the presence of phytate and polyphenols which inhibits Fe absorption. In the present study, the genetic variability and heritability for seed Fe and Zn content was studied. The effect of genotypes was significant for all the quality traits indicating presence of enough variability among the blackgram genotypes for the traits. The Fe content in 26 blackgram genotypes ranged from 71.02 to 100.20 ppm, whereas Zn content ranged from 18...
March 2017: Journal of Food Science and Technology
https://www.readbyqxmd.com/read/28292906/parasitophorous-vacuole-poration-precedes-its-rupture-and-rapid-host-erythrocyte-cytoskeleton-collapse-in-plasmodium-falciparum-egress
#7
Victoria L Hale, Jean M Watermeyer, Fiona Hackett, Gema Vizcay-Barrena, Christiaan van Ooij, James A Thomas, Matthew C Spink, Maria Harkiolaki, Elizabeth Duke, Roland A Fleck, Michael J Blackman, Helen R Saibil
In the asexual blood stages of malarial infection, merozoites invade erythrocytes and replicate within a parasitophorous vacuole to form daughter cells that eventually exit (egress) by sequential rupture of the vacuole and erythrocyte membranes. The current model is that PKG, a malarial cGMP-dependent protein kinase, triggers egress, activating malarial proteases and other effectors. Using selective inhibitors of either PKG or cysteine proteases to separately inhibit the sequential steps in membrane perforation, combined with video microscopy, electron tomography, electron energy loss spectroscopy, and soft X-ray tomography of mature intracellular Plasmodium falciparum parasites, we resolve intermediate steps in egress...
March 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28286139/de-novo-transcriptome-sequencing-and-analysis-of-the-juvenile-and-adult-stages-of-fasciola-gigantica
#8
Xiao-Xuan Zhang, Wei Cong, Hany M Elsheikha, Guo-Hua Liu, Jian-Gang Ma, Wei-Yi Huang, Quan Zhao, Xing-Quan Zhu
Fasciola gigantica is regarded as the major liver fluke causing fasciolosis in livestock in tropical countries. Despite the significant economic and public health impacts of F. gigantica there are few studies on the pathogenesis of this parasite and our understanding is further limited by the lack of genome and transcriptome information. In this study, de novo Illumina RNA sequencing (RNA-seq) was performed to obtain a comprehensive transcriptome profile of the juvenile (42days post infection) and adult stages of F...
March 9, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28279024/contribution-of-the-cyclic-nucleotide-gated-channel-subunit-cng-3-to-olfactory-plasticity-in-caenorhabditis-elegans
#9
Damien M O'Halloran, Svetlana Altshuler-Keylin, Xiao-Dong Zhang, Chao He, Christopher Morales-Phan, Yawei Yu, Julia A Kaye, Chantal Brueggemann, Tsung-Yu Chen, Noelle D L'Etoile
In Caenorhabditis elegans, the AWC neurons are thought to deploy a cGMP signaling cascade in the detection of and response to AWC sensed odors. Prolonged exposure to an AWC sensed odor in the absence of food leads to reversible decreases in the animal's attraction to that odor. This adaptation exhibits two stages referred to as short-term and long-term adaptation. Previously, the protein kinase G (PKG), EGL-4/PKG-1, was shown necessary for both stages of adaptation and phosphorylation of its target, the beta-type cyclic nucleotide gated (CNG) channel subunit, TAX-2, was implicated in the short term stage...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28273832/more-insight-into-bdnf-against-neurodegeneration-anti-apoptosis-anti-oxidation-and-suppression-of-autophagy
#10
REVIEW
Shang-Der Chen, Chia-Lin Wu, Wei-Chao Hwang, Ding-I Yang
In addition to its well-established neurotrophic action, brain-derived neurotrophic factor (BDNF) also possesses other neuroprotective effects including anti-apoptosis, anti-oxidation, and suppression of autophagy. We have shown before that BDNF triggers multiple mechanisms to confer neuronal resistance against 3-nitropropionic acid (3-NP)-induced mitochondrial dysfunction in primary rat cortical cultures. The beneficial effects of BDNF involve the induction of anti-oxidative thioredoxin with the resultant expression of anti-apoptotic B-cell lymphoma 2 (Bcl-2) as well as erythropoietin (EPO)-dependent stimulation of sonic hedgehog (SHH)...
March 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28263955/pathway-cross-talk-analysis-in-detecting-significant-pathways-in-barrett-s-esophagus-patients
#11
Zhengyuan Xu, Yan Yan, Jian He, Xinfang Shan, Weiguo Wu
BACKGROUND The pathological mechanism of Barrett's esophagus (BE) is still unclear. In the present study, pathway cross-talks were analyzed to identify hub pathways for BE, with the purpose of finding an efficient and cost-effective detection method to discover BE at its early stage and take steps to prevent its progression. MATERIAL AND METHODS We collected and preprocessed gene expression profile data, original pathway data, and protein-protein interaction (PPI) data. Then, we constructed a background pathway cross-talk network (BPCN) based on the original pathway data and PPI data, and a disease pathway cross-talk network (DPCN) based on the differential pathways between the PPI data and the BE and normal control...
March 6, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28263796/insulin-increases-filtration-barrier-permeability-via-trpc6-dependent-activation-of-pkgi%C3%AE-signaling-pathways
#12
Dorota Rogacka, Irena Audzeyenka, Patrycja Rachubik, Michał Rychłowski, Małgorzata Kasztan, Maciej Jankowski, Stefan Angielski, Agnieszka Piwkowska
Podocytes are dynamic polarized cells on the surface of glomerular capillaries and an essential component of the glomerular filtration barrier. Insulin increases the activation of protein kinase G type Iα (PKGIα) subunits, leading to podocyte dysfunction. In addition, accumulating evidence suggests that TRPC6 channels are crucial mediators of podocyte calcium handling and involved in the regulation of glomerular filtration. Therefore, we investigated whether TRPC6 is involved in the regulation of filtration barrier permeability by insulin via the PKGIα-dependent manner...
March 2, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28242257/exendin-4-inhibits-structural-remodeling-and-improves-ca-2-homeostasis-in-rats-with-heart-failure-via-the-glp-1-receptor-through-the-enos-cgmp-pkg-pathway
#13
Jingjing Chen, Dandan Wang, Fangai Wang, Shaobo Shi, Yuting Chen, Bo Yang, Yanhong Tang, Congxin Huang
The glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 is a long-acting analog of GLP-1, which stimulates insulin secretion and is clinically used in the treatment of type 2 diabetes. Previous studies have demonstrated that GLP-1 agonists and analogs serve as cardioprotective factors in various conditions. Disturbances in calcium cycling are characteristic of heart failure (HF); therefore, the aim of this study was to investigate the effect of exendin-4 (a GLP-1 mimetic) on the regulation of calcium handling and to identify the underlying mechanisms in an HF rat model after myocardial infarction (MI)...
April 2017: Peptides
https://www.readbyqxmd.com/read/28229930/atrial-natriuretic-peptide-a-novel-mediator-for-tgf-%C3%AE-1-induced-epithelial-mesenchymal-transition-in-16hbe-14o-and-a549-cells
#14
Shuyuan Chu, Xiufeng Zhang, Yabing Sun, Yuanyuan Yu, Yaxi Liang, Ming Jiang, Jianwei Huang, Libing Ma
Atrial natriuretic peptide (ANP) is increasingly expressed on airway and inhibits pulmonary arterial remodeling. However, the role of ANP in remodeling of respiratory system is still unclear. The role of ANP on airway remodeling and the possible mechanism was explored in this study. Both human bronchial epithelial 16HBE-14o cells and alveolar epithelial A549 cells were stimulated by TGF-β1, ANP, cGMP inhibitor, PKG inhibitor, and cGMP analogue. The expressions of epithelial markers, mesenchymal markers, and Smad3 were assessed by quantitative real-time PCR and western blotting...
February 13, 2017: Peptides
https://www.readbyqxmd.com/read/28181511/natriuretic-peptide-receptor-b-modulates-the-proliferation-of-the-cardiac-cells-expressing-the-stem-cell-antigen-1
#15
Stéphanie Rignault-Clerc, Christelle Bielmann, Lucas Liaudet, Bernard Waeber, François Feihl, Nathalie Rosenblatt-Velin
Brain Natriuretic Peptide (BNP) injections in adult "healthy" or infarcted mice led to increased number of non-myocyte cells (NMCs) expressing the nuclear transcription factor Nkx2.5. The aim of this study was to identify the nature of the cells able to respond to BNP as well as the signaling pathway involved. BNP treatment of neonatal mouse NMCs stimulated Sca-1(+) cell proliferation. The Sca-1(+) cells were characterized as being a mixed cell population involving fibroblasts and multipotent precursor cells...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28124739/the-regulation-of-transient-receptor-potential-canonical-4-trpc4-channel-by-phosphodiesterase-5-inhibitor-via-the-cyclic-guanosine-3-5-monophosphate
#16
Jinhong Wie, SeungJoo Jeong, Misun Kwak, Jongyun Myeong, MeeRee Chae, Jong Kwan Park, Sung Won Lee, Insuk So
The transient receptor potential (TRP) protein superfamily consists of a diverse group of cation channels that bear structural similarities to the fruit fly Drosophila TRP. The TRP superfamily is distinct from other groups of ion channels in displaying a large diversity in ion selectivity, modes of activation, and physiological functions. Classical TRP (transient receptor potential canonical (TRPC)) channels are activated by stimulation of Gq-PLC-coupled receptors and modulated by phosphorylation. The cyclic guanosine monophosphate (cGMP)-PKG pathway is involved in the regulation of TRPC3 and TRPC6 channels...
January 26, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28099939/type-5-phosphodiesterase-regulates-glioblastoma-multiforme-aggressiveness-and-clinical-outcome
#17
Valeriana Cesarini, Maurizio Martini, Lucia Ricci Vitiani, Giovanni Luca Gravina, Silvia Di Agostino, Grazia Graziani, Quintino Giorgio D'Alessandris, Roberto Pallini, Luigi M Larocca, Pellegrino Rossi, Emmanuele A Jannini, Susanna Dolci
Expression of type 5 phosphodiesterase (PDE5), a cGMP-specific hydrolytic enzyme, is frequently altered in human cancer, but its specific role in tumorigenesis remains controversial. Herein, by analyzing a cohort of 69 patients affected by glioblastoma multiforme (GBM) who underwent chemo- and radiotherapy after surgical resection of the tumor, we found that PDE5 was strongly expressed in cancer cells in about 50% of the patients. Retrospective analysis indicated that high PDE5 expression in GBM cells significantly correlated with longer overall survival of patients...
February 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088782/pde5-inhibitors-enhance-the-lethality-of-pemetrexed-sorafenib
#18
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Paul Dent
The combination of pemetrexed and sorafenib has significant clinical activity against a wide variety of tumor types in patients and the present studies were performed to determine whether sildenafil enhances the killing potential of [pemetrexed + sorafenib]. In multiple genetically diverse lung cancer cell lines, sildenafil enhanced the lethality of [pemetrexed + sorafenib]. The three-drug combination reduced the activities of AKT, mTOR and STAT transcription factors; increased the activities of eIF2α and ULK-1; lowered the expression of MCL-1, BCL-XL, thioredoxin and SOD2; and increased the expression of Beclin1...
February 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28077315/inhibition-of-inos-alleviates-cognitive-deficits-and-depression-in-diabetic-mice-through-downregulating-the-no-sgc-cgmp-pkg-signal-pathway
#19
Xiao Yan Zhou, Fang Zhang, Chang Jiang Ying, Jing Chen, Ling Chen, Jing Dong, Yue Shi, Mang Tang, Xiao Tong Hu, Zhi Hua Pan, Na Na Xu, Kui Yang Zheng, Ren Xian Tang, Yuan Jian Song
Diabetes mellitus often results in a number of complications involving impaired brain function, including cognitive deficits and depression. However, the potential mechanisms for diabetes-related cognitive deficits and depression are not fully understood. Neurons in the hippocampal, cortical and amygdala functional regions are more susceptible to damage during hyperglycemia. Neuroprotection in the brain can rescue cognitive deficits and depression induced by hyperglycemia. This study investigated the potential mechanisms underlying diabetes-related congnitive deficits and depression, determined whether the inflammatory factor inducible nitric oxide synthase (iNOS) and the nitric oxide (NO)/soluble guanylyl cyclases (sGC)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) pathway, play key roles in cognitive deficits and depression associated...
January 8, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28065754/mechanisms-involved-in-antinociception-induced-by-a-polysulfated-fraction-from-seaweed-gracilaria-cornea-in-the-temporomandibular-joint-of-rats
#20
Chistiane Oliveira Coura, Hellíada Vasconcelos Chaves, Danielle Rocha do Val, Lorena Vasconcelos Vieira, Felipe Dantas Silveira, Fernanda Maxcynne Lino Dos Santos Lopes, Francisco Isaac Fernandes Gomes, Annyta Fernandes Frota, Ricardo Basto Souza, Juliana Trindade Clemente-Napimoga, Mirna Marques Bezerra, Norma Maria Barros Benevides
Temporomandibular disorder is a common clinical condition involving pain in the temporomandibular joint (TMJ) region. This study assessed the antinociceptive effects of a polysulfated fraction from the red seaweed Gracilaria cornea (Gc-FI) on the formalin-induced TMJ hypernociception in rats and investigated the involvement of different mechanisms. Male Wistar rats were pretreated with injection (sc) of saline or Gc-FI 1h before intra- TMJ injection of formalin to evaluate the nociception. The results showed that pretreatment with Gc-FI significantly reduced formalin-induced nociceptive behavior...
April 2017: International Journal of Biological Macromolecules
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