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https://www.readbyqxmd.com/read/29237539/cdkn2a-deficiency-promotes-adipose-tissue-browning
#1
Nabil Rabhi, Sarah Anissa Hannou, Xavier Gromada, Elisabet Salas, Xi Yao, Frédérik Oger, Charlène Carney, Isabel C Lopez-Mejia, Emmanuelle Durand, Iandry Rabearivelo, Amélie Bonnefond, Emilie Caron, Lluis Fajas, Christian Dani, Philippe Froguel, Jean-Sébastien Annicotte
OBJECTIVES: Genome-wide association studies have reported that DNA polymorphisms at the CDKN2A locus modulate fasting glucose in human and contribute to type 2 diabetes (T2D) risk. Yet the causal relationship between this gene and defective energy homeostasis remains elusive. Here we sought to understand the contribution of Cdkn2a to metabolic homeostasis. METHODS: We first analyzed glucose and energy homeostasis from Cdkn2a-deficient mice subjected to normal or high fat diets...
December 1, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29233660/negative-inotropic-effects-of-diadenosine-tetraphosphate-are-mediated-by-protein-kinase-c-and-phosphodiesterases-stimulation-in-the-rat-heart
#2
Nikolai Pakhomov, Ksenia Pustovit, Victoria Potekhina, Tatiana Filatova, Vladislav Kuzmin, Denis Abramochkin
Extracellular diadenosine polyphosphates (ApnA) are recently considered as an endogenous signaling compounds with transmitter-like activity which present in numerous tissues, including heart. It has been demonstrated previously that extracellular ApnA cause alteration of the heart functioning via purine receptors in different mammalian species. Nevertheless, principal intracellular pathways which underlie ApnA action in the heart remain unknown. In the present study the role of the P2Y-associated intracellular regulatory pathway in the mediation of diadenosine tetraphosphate (Ap4A) effects in the rat heart has been investigated for the first time...
December 9, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29196237/melatonin-protects-diabetic-heart-against-ischemia-reperfusion-injury-role-of-membrane-receptor-dependent-cgmp-pkg-activation
#3
Li-Ming Yu, Wen-Cheng Di, Xue Dong, Zhi Li, Yong Zhang, Xiao-Dong Xue, Yin-Li Xu, Jian Zhang, Xiong Xiao, Jin-Song Han, Yu Liu, Yang Yang, Hui-Shan Wang
It has been demonstrated that the anti-oxidative and cardioprotective effects of melatonin are, at least in part, mediated by its membrane receptors. However, the direct downstream signaling remains unknown. We previously found that melatonin ameliorated myocardial ischemia-reperfusion (MI/R) injury in diabetic animals, although the underlying mechanisms are also incompletely understood. This study was designed to determine the role of melatonin membrane receptors in melatonin's cardioprotective actions against diabetic MI/R injury with a focus on cGMP and its downstream effector PKG...
November 30, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29192457/-pharmacological-mechanism-analysis-of-oligopeptide-from-pinctada-fucata-based-on-in-silico-proteolysis-and-protein-interaction-network
#4
Jin-Long Duan, Kui-Wu Yao, Xiao-Xiao Feng, Jue Cao, Zhou Yu
Thoracic obstruction is mainly attributed to the scope of coronary heart disease in modern medicine, and traditional Chinese medicine(TCM) shows a significant effect in the treatment of thoracic obstruction. In this research, a network pharmacology method was carried out to systemically study the underlying mechanism of the core herbal compatibility in TCM on the thoracic obstruction. First, we collected the literature about TCM prescriptions for treating thoracic obstruction from CNKI. Then, a prescription database was establish by TCM inheritance support platform system(V2...
September 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29182561/analysis-of-microrna-expression-in-newborns-with-differential-birth-weight-using-newborn-screening-cards
#5
Patricia Rodil-Garcia, Elvira Del Carmen Arellanes-Licea, Angélica Montoya-Contreras, Luis A Salazar-Olivo
Birth weight is an early predictor for metabolic diseases and microRNAs (miRNAs) are proposed as fetal programming participants. To evaluate the use of dried blood spots (DBS) on newborn screening cards (NSC) as a source of analyzable miRNAs, we optimized a commercial protocol to recover total miRNA from normal birth weight (NBW, n = 17-20), low birth weight (LBW, n = 17-20) and high birth weight (macrosomia, n = 17-20) newborns and analyzed the relative expression of selected miRNAs by stem-loop RT-qPCR. The possible role of miRNAs on the fetal programming of metabolic diseases was explored by bioinformatic tools...
November 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29175000/cyclic-nucleotide-signaling-changes-associated-with-normal-aging-and-age-related-diseases-of-the-brain
#6
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/29169825/nitric-oxide-cgmp-pkg-signaling-in-the-bed-nucleus-of-the-stria-terminalis-modulates-the-cardiovascular-responses-to-stress-in-male-rats
#7
Lucas Barretto-de-Souza, Mariane B Adami, Leandro A Oliveira, Lucas Gomes-de-Souza, Josiane O Duarte, Jeferson Almeida, Carlos C Crestani
The bed nucleus of the stria terminalis (BNST) constitutes an important component of neural substrates of physiological and behavioral responses to aversive stimuli, and it has been implicated on cardiovascular responses evoked by stress. Nevertheless, the local neurochemical mechanisms involved in BNST control of cardiovascular responses during aversive threats are still poorly understood. Thus, the aim of the present study was to assess the involvement of activation in the BNST of the neuronal isoform of the enzyme nitric oxide synthase (nNOS), as well as of signaling mechanisms related to nitric oxide effects such as soluble guanylate cyclase (sGC) and protein kinase G (PKG) on cardiovascular responses induced by an acute session of restraint stress in male rats...
November 20, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29150923/pkg-ii-effectively-reversed-egf-induced-protein-expression-alterations-in-human-gastric-cancer-cell-lines
#8
Hai Qian, Yan Tao, Lu Jiang, Ying Wang, Ting Lan, Min Wu, Ji Pang, Kwaku Appiah-Kubi, Yongchang Chen, Yan Wu
Epidermal growth factor receptor (EGFR) plays an important role in gastric cancer (GC) progression. Our previous data demonstrated that type II cGMP-dependent protein kinase (PKG II) could block the EGF-EGFR axis as well as down-stream signaling pathways for example, MAPK, PI3K and PLC in gastric cancer cells. However, the exact mechanisms of PKG II against cancer remain unclear. Therefore, the present work was to address the above question. Human gastric cancer cell line AGS was infected with adenoviral construct encoding cDNA of PKG II (Ad-PKG II) to up-regulate PKG II and then treated with 8-pCPT-cGMP...
November 18, 2017: Cell Biology International
https://www.readbyqxmd.com/read/29150274/neuroprotective-potential-of-high-dose-biotin
#9
Mark F McCarty, James J DiNicolantonio
A recent controlled trial has established that high-dose biotin supplementation - 100 mg, three times daily - has a stabilizing effect on progression of multiple sclerosis (MS). Although this effect has been attributed to an optimization of biotin's essential cofactor role in the brain, a case can be made that direct stimulation of soluble guanylate cyclase (sGC) by pharmacological concentrations of biotin plays a key role in this regard. The utility of high-dose biotin in MS might reflect an anti-inflammatory effect of cGMP on the cerebral microvasculature, as well on oligodendrocyte differentiation and on Schwann cell production of neurotrophic factors thought to have potential for managing MS...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29138357/tadalafil-a-long-acting-phosphodiesterase-inhibitor-promotes-bone-marrow-stem-cell-survival-and-their-homing-into-ischemic-myocardium-for-cardiac-repair
#10
Ibrahim Elmadbouh, Muhammad Ashraf
The aim was to evaluate the tadalafil-mediated effects at molecular level on bone marrow-derived mesenchymal stem cells (MSCs) survival and their homing into the infarcted hearts to promote cardiac repair and improve function. MSCs were pretreated in vitro with inhibitors of PKG, MAPK, FasL, nitric oxide synthase (NOS) (L-NAME), CXCR4 (AMD3100), or miR-21 inhibitors (+/-luciferase construction +/-Fas) prior to tadalafil treatment for 2 h. These MSCs were then subjected to H2O2 stress to assess their injury...
November 2017: Physiological Reports
https://www.readbyqxmd.com/read/29132129/administration-of-curcumin-protects-kidney-tubules-against-renal-ischemia-reperfusion-injury-riri-by-modulating-nitric-oxide-no-signaling-pathway
#11
Fuhe Liu, Wenjuan Ni, Jiajia Zhang, Guokang Wang, Fanzhu Li, Wenxia Ren
BACKGROUND/AIMS: To explore the protective effect of curcumin on renal ischemia-reperfusion injury (RIRI) in rats, and its influence on nephridial tissue's NO and cGMP levels as well as downstream signaling pathway, to elucidate the possible mechanism of curcumin on RIRI. METHODS: 36 Sprague Dawley rats (SD rats) were randomly divided into Sham group, Model group, curcumin (CUR +) Model group, 12 rats per group. They were all given RIRI model preparation by unilateral artery occlusion method...
November 13, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29131824/predictive-model-identifies-key-network-regulators-of-cardiomyocyte-mechano-signaling
#12
Philip M Tan, Kyle S Buchholz, Jeffrey H Omens, Andrew D McCulloch, Jeffrey J Saucerman
Mechanical strain is a potent stimulus for growth and remodeling in cells. Although many pathways have been implicated in stretch-induced remodeling, the control structures by which signals from distinct mechano-sensors are integrated to modulate hypertrophy and gene expression in cardiomyocytes remain unclear. Here, we constructed and validated a predictive computational model of the cardiac mechano-signaling network in order to elucidate the mechanisms underlying signal integration. The model identifies calcium, actin, Ras, Raf1, PI3K, and JAK as key regulators of cardiac mechano-signaling and characterizes crosstalk logic imparting differential control of transcription by AT1R, integrins, and calcium channels...
November 13, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29111666/switching-cyclic-nucleotide-selective-activation-of-pka-holoenzyme-reveals-distinct-roles-of-tandem-cnb-domains
#13
Daniel He, Robin Lorenz, Choel Kim, Friedrich W Herberg, Chinten James Lim
The cAMP- and cGMP-dependent protein kinases (PKA and PKG) are key effectors of cyclic nucleotide signaling. Both share structural features that include tandem cyclic nucleotide-binding (CNB) domains, CNB-A and CNB-B, yet their functions are separated through preferential activation by either cAMP or cGMP. Based on structural studies and modeling, key CNB contact residues have been identified for both kinases. In this study, we explored the requirements for conversion of PKA activation from cAMP-dependent to cGMP-dependent...
November 7, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/29101001/icariside-ii-a-pde5-inhibitor-from-epimedium-brevicornum-promotes-neuron-like-pheochromocytoma-pc12-cell-proliferation-via-activating-no-cgmp-pkg-pathway
#14
Jianmei Gao, Yingshu Xu, Ming Lei, Jingshan Shi, Qihai Gong
Icariside II (ICS II), a phosphodiesterase 5 inhibitor (PDE 5-I), is a major ingredient of Epimedium brevicornum, with wide spectrum of neuroprotective properties. However, little is known about the potential beneficial effect of ICS II on neuronal cell proliferation, and its possible underlying mechanism remains still unclear. We hypothesized that the beneficial effect of ICS II on neuron-like highly differentiated rat pheochromocytoma (PC12) cell proliferation is correlated with the nitric oxide (NO) signaling pathway and its upstream of PI3K/AKT pathway...
October 31, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29071734/nitric-oxide-is-required-for-the-insulin-sensitizing-effects-of-contraction-in-mouse-skeletal-muscle
#15
Xinmei Zhang, Danielle Hiam, Yet-Hoi Hong, Anthony Zulli, Alan Hayes, Stephen Rattigan, Glenn K McConell
The factors regulating the increase in skeletal muscle insulin sensitivity after exercise are unclear. We examined whether nitric oxide (NO) is required for the increase in insulin sensitivity after ex vivo contractions. Isolated C57BL/6J mouse EDL muscles were contracted for 10 min or remained at rest (basal) with or without the NO synthase (NOS) inhibition (L-NMMA; 100 μm). 3.5 h post contraction/basal, muscles were exposed to saline or insulin (120 μU ml(-1) ) with or without L-NMMA during the last 30 min...
October 25, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29067241/effect-of-phosphodiesterase-5-inhibitors-on-glycemic-control-in-person-with-type-2-diabetes-mellitus-a-systematic-review-and-meta-analysis
#16
Nalinee Poolsup, Naeti Suksomboon, Nandar Aung
Chronic use of phosphodiesterase-5 inhibitors (PDE-5i) has been shown to improve insulin action on muscle glucose uptake by the prolongation of nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase (PKG) signalling. AIMS: As the effects of PDE-5i on glycemic control in person with type 2 diabetes mellitus (T2DM) have not been systematically explored, we conducted a meta-analysis of available randomized controlled trials (RCTs). METHODS: A literature search was performed through electronic databases including MEDLINE (Pubmed), The Cochrane Library, SCOPUS, Web of Science, CINAHL, www...
December 2016: Journal of Clinical & Translational Endocrinology
https://www.readbyqxmd.com/read/29054855/h-ras-deletion-protects-against-angiotensin-ii-induced-arterial-hypertension-and-cardiac-remodeling-through-protein-kinase-g-i%C3%AE-pathway-activation
#17
Paloma Martín-Sánchez, Alicia Luengo, Mercedes Griera, María Jesús Orea, Marina López-Olañeta, Antonio Chiloeches, Enrique Lara-Pezzi, Sergio de Frutos, Manuel Rodríguez-Puyol, Laura Calleros, Diego Rodríguez-Puyol
Ras proteins regulate cell survival, growth, differentiation, blood pressure, and fibrosis in some organs. We have demonstrated that H-ras gene deletion produces mice hypotension via a soluble guanylate cyclase-protein kinase G (PKG)-dependent mechanism. In this study, we analyzed the consequences of H-ras deletion on cardiac remodeling induced by continuous angiotensin II (AngII) infusion and the molecular mechanisms implied. Left ventricular posterior wall thickness and mass and cardiomyocyte cross-sectional area were similar between AngII-treated H-Ras knockout (H-ras(-/-) ) and control wild-type (H-ras(+/+) ) mice, as were extracellular matrix protein expression...
October 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29050202/phosphodiesterase-10a-is-overexpressed-in-lung-tumor-cells-and-inhibitors-selectively-suppress-growth-by-blocking-%C3%AE-catenin-and-mapk-signaling
#18
Bing Zhu, Ashley Lindsey, Nan Li, Kevin Lee, Veronica Ramirez-Alcantara, Joshua C Canzoneri, Alexandra Fajardo, Luciana Madeira da Silva, Meagan Thomas, John T Piazza, Larry Yet, Brian T Eberhardt, Evrim Gurpinar, Dennis Otali, William Grizzle, Jacob Valiyaveettil, Xi Chen, Adam B Keeton, Gary A Piazza
Phosphodiesterase 10A (PDE10) is a cyclic nucleotide (e.g. cGMP) degrading enzyme highly expressed in the brain striatum where it plays an important role in dopaminergic neurotransmission, but has limited expression and no known physiological function outside the central nervous system. Here we report that PDE10 mRNA and protein levels are strongly elevated in human non-small cell lung cancer cells and lung tumors compared with normal human airway epithelial cells and lung tissue, respectively. Genetic silencing of PDE10 or inhibition by small molecules such as PQ10 was found to selectively inhibit the growth and colony formation of lung tumor cells...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29049001/effects-of-melatonin-on-mechanisms-involved-in-hypertension-using-human-umbilical-vein-endothelial-cells
#19
Guangfang Shao, Suping Zhang, Jihua Nie, Jianxiang Li, Jian Tong
Changes in diurnal rhythmicity in blood pressure (BP) are associated with hypertension and consequent cardiovascular damage. The involvement of diurnal rhythmicity as a pathogenic factor in hypertension is not fully understood. Since the hormone melatonin (MLT) regulates circadian rhythm, it was also of interest to determine whether this hormone played a role in hypertension-related alterations in circadian rhythm. Thus the aim of this study was to examine the mechanisms underlying MLT-mediated antihypertension...
October 19, 2017: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/29046298/identification-of-dual-mechanisms-mediating-5-hydroxytryptamine-receptor-1f-induced-mitochondrial-biogenesis
#20
Whitney S Gibbs, Sara M Garrett, Craig C Beeson, Rick G Schnellmann
Our laboratory recently made the novel observation that 5-hydroxytryptamine 1F (5-HT1F) receptor activation induces mitochondrial biogenesis (MB), the production of new, functional mitochondria, in vitro and vivo. We sought to determine the mechanism linking the 5-HT1F receptor to MB in renal proximal tubule cells. Using LY344864, a selective 5-HT1F receptor agonist, we determined that the 5-HT1F receptor is coupled to Gαi/o and induces MB through Gβγ dependent activation of Akt, endothelial nitric oxide (eNOS), cyclic guanosine-monophosphate (cGMP), protein kinase G (PKG) and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α)...
October 18, 2017: American Journal of Physiology. Renal Physiology
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