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https://www.readbyqxmd.com/read/27925190/s100a1-and-s100b-calcium-sensors-at-the-cross-roads-of-multiple-chondrogenic-pathways
#1
REVIEW
José Diaz-Romero, Dobrila Nesic
The S100 protein family comprises more than 20 members of small calcium binding proteins operating as Ca2 + -activated switches that interact and modulate the activity of a large number of targets. S100A1 and S100B, two members of this family, have been recently associated with the differentiation status of human articular chondrocytes. Both proteins are homogeneously expressed in all cartilage zones, their expression decreases during chondrocyte dedifferentiation, and can be induced under conditions promoting redifferentiation...
December 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27923813/the-chemical-basis-of-thiol-addition-to-nitro-conjugated-linoleic-acid-a-protective-cell-signaling-lipid
#2
Lucia Turell, Dario A Vitturi, E Laura Coitiño, Lourdes Lebrato, Matias N Moller, Camila Sagasti, Sonia R Salvatore, Steven R Woodcock, Beatriz Alvarez, Francisco J Schopfer
Nitroalkene fatty acids are formed in vivo and exert protective and anti-inflammatory effects via reversible Michael addition to thiol-containing proteins in key signaling pathways. Nitro-conjugated linoleic acid (NO2-CLA) is preferentially formed, constitutes the most abundant nitrated fatty acid in humans and contains two carbons that could potentially react with thiols, modulating signaling actions and levels. In this work, we examined the reactions of NO2-CLA with low molecular weight thiols (glutathione, cysteine, homocysteine, cysteinylglycine and β mercaptoethanol) and human serum albumin (HSA)...
December 6, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27923791/reduced-density-and-altered-regulation-of-rat-atrial-l-type-ca2-current-in-rat-heart-failure
#3
Richard C Bond, Simon M Bryant, Judy J Watson, Jules C Hancox, Clive H Orchard, Andrew F James
Atrial L-type Ca(2+) current (ICaL) downregulation in heart failure contributes to the pathogenesis of atrial fibrillation and is proposed to involve reduction in channel phosphorylation by PKA. The regulation of atrial ICaL was examined in heart failure. Anesthetized adult male Wistar rats underwent surgical coronary artery ligation (CAL, N=10) or equivalent sham-operation (Sham, N=12). Left atrial myocytes were isolated ~18 weeks post-surgery and whole-cell currents recorded (holding potential=-80 mV). ICaL activated by depolarizing pulses to voltages from -40 to +50 mV were normalized to cell capacitance and current density-voltage relations plotted...
December 6, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27921081/a-fungus-specific-protein-domain-is-essential-for-rasa-mediated-morphogenetic-signaling-in-aspergillus-fumigatus
#4
Qusai Al Abdallah, Tiffany S Norton, Amy M Hill, Lawrence L LeClaire, Jarrod R Fortwendel
Ras proteins function as conserved regulators of eukaryotic growth and differentiation and are essential signaling proteins orchestrating virulence in pathogenic fungi. Here, we report the identification of a novel N-terminal domain of the RasA protein in the filamentous fungus Aspergillus fumigatus. Whereas this domain is absent in Ras homologs of higher eukaryotes, the N-terminal extension is conserved among fungi and is characterized by a short string of two to eight amino acids terminating in an invariant arginine...
November 2016: MSphere
https://www.readbyqxmd.com/read/27919636/adrenomedullin-and-angiotensin-ii-signaling-pathways-involved-in-the-effects-on-cerebellar-antioxidant-enzymes-activity
#5
Figueira Leticia, Israel Anita
Human adrenomedullin (AM) is a 52-amino acid peptide involved in cardiovascular control. AM has two specific receptors formed by the calcitonin-receptor-like receptor (CRLR) and receptor activity-modifying protein (RAMP) 2 or 3, known as AM1 and AM2 receptors, respectively. In addition, AM has appreciable affinity for the calcitonin gene-1 related peptide receptor (CGRP1), composed of CRLR/RAMP1. In brain, AM and their receptors are expressed in several localized areas, including the cerebellum. AM has been reported as an antioxidant...
December 2, 2016: Brain Research Bulletin
https://www.readbyqxmd.com/read/27919519/investigation-of-the-acid-base-and-electromigration-properties-of-5-azacytosine-derivatives-using-capillary-electrophoresis-and-density-functional-theory-calculations
#6
Denisa Geffertová, Syed Tahir Ali, Veronika Šolínová, Marcela Krečmerová, Antonín Holý, Zdeněk Havlas, Václav Kašička
Capillary electrophoresis (CE) and quantum mechanical density functional theory (DFT) were applied to the investigation of the acid-base and electromigration properties of important compounds: newly synthesized derivatives of 5-azacytosine - analogs of efficient antiviral drug cidofovir. These compounds exhibit a strong antiviral activity and they are considered as potential new antiviral agents. For their characterization and application, it is necessary to know their acid-base properties, particularly the acidity constants (pKa) of their ionogenic groups (the basic N(3) atom of the triazine ring and the acidic phosphonic acid group in the alkyl chain)...
November 29, 2016: Journal of Chromatography. A
https://www.readbyqxmd.com/read/27918617/thermodynamic-insights-on-a-bistable-acid-base-switchable-molecular-shuttle-with-strongly-shifted-co-conformational-equilibria
#7
Giulio Ragazzon, Alberto Credi, Benoit Colasson
Bistable [2]rotaxanes in which the affinities of the two stations can be reversed form the basis of molecular shuttles. Gaining quantitative information on such rotaxanes in which the ring distribution between the two stations is largely nonsymmetric has proven to be very challenging. Here we report on two independent experimental methodologies - based on luminescence lifetime measurement and acid-base titrations - to determine the relative populations of the two co-conformations of a [2]rotaxane. The assays yield convergent results and are sensitive enough to measure an equilibrium constant (K ~ 4000) out of reach for NMR spectroscopy...
December 5, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27917591/the-pde4-inhibitor-roflumilast-reduces-weight-gain-by-increasing-energy-expenditure-and-leads-to-improved-glucose-metabolism
#8
Julia Möllmann, Florian Kahles, Corinna Lebherz, Ben Kappel, Christer Baeck, Frank Tacke, Christian Werner, Massimo Federici, Nikolaus Marx, Michael Lehrke
AIMS: The PDE4 inhibitor roflumilast is a clinically approved anti-inflammatory drug used for the treatment of chronic obstructive pulmonary disease. In addition, roflumilast was found to reduce body weight and improve glucose metabolism by a yet unknown mechanism. MATERIALS AND METHODS: Metabolic effects of roflumilast were investigated in C57BL/6J mice on high fat western-type diet treated with or without roflumilast for a period of 12 weeks. RESULTS: Roflumilast led to a marked reduction of body weight gain, which became apparent in the second week following treatment initiation and was attributable to a pronounced increase of energy expenditure...
December 5, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27915191/rp-hplc-determination-of-dissociation-constant-using-solely-aqueous-mobile-phase
#9
Tereza Volná, Kamil Motyka, Jan Hlaváč
The proposed HPLC method using solely or nearly 100% aqueous mobile buffer as mobile phase offers fast determination of dissociation constant for compounds in relatively wide range of lipophilicity (log P from -2.26 to 2.26). The dissociation constant value for simpler chemical compounds can be determined via only 8 chromatographic runs. The number of needed chromatographic separations depends on the structural complexity of the tested compound. Moreover, the proposed method does not require a measurement of Yasuda-Shedlovsky extrapolation that includes several pKa determinations in solutions with different methanol content which speeds up considerably the procedure...
November 27, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/27915021/poly-aspartic-acid-with-adjustable-ph-dependent-solubility
#10
Csaba Németh, Benjámin Gyarmati, Timur Abdullin, Krisztina László, András Szilágyi
Poly(aspartic acid) (PASP) derivatives with adjustable pH-dependent solubility were synthesized and characterized to establish the relationship between their structure and solubility in order to predict their applicability as a basic material for enteric coatings. Polysuccinimide, the precursor of PASP, was modified with short chain alkylamines, and the residual succinimide rings were subsequently opened to prepare the corresponding PASP derivatives. Study of the effects of the type and concentration of the side groups on the pH-dependent solubility of PASP showed that solubility can be adjusted by proper selection of the chemical structure...
November 30, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27913186/protein-kinase-a-activation-by-retinoic-acid-in-the-nuclei-of-hl60-cells
#11
Asako Sakai, Masahiko Imai, Katsuhiko Takahashi, Shinya Hasegawa, Masahiro Yamasaki, Toshihiro Ohba, Noriko Takahashi
BACKGROUND: Activation of protein kinase A (PKA) occurs during retinoic acid (RA)-induced granulocytic differentiation of human promyelocytic leukemia HL60 cells. It is known that the RIIα regulatory subunit of PKA, is modified by RA (retinoylated) in the early stages of differentiation. We have investigated the effects of RA on PKA during cell differentiation in order to understand the potential significance of this process in the retinoylation of RIIα subunits. METHODS: Immunoblotting, immunoprecipitation, confocal microscopy, PCR, and PKA activity assays were employed for characterizing the effects of RA on PKA...
November 29, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27911956/adenosine-stimulate-proliferation-and-migration-in-triple-negative-breast-cancer-cells
#12
Miriam Fernandez-Gallardo, Ricardo González-Ramírez, Alejandro Sandoval, Ricardo Felix, Eduardo Monjaraz
Emerging evidence suggests that the adenosine (Ado) receptors may play crucial roles in tumor progression. Here, we show that Ado increases proliferation and migration in a triple negative breast cancer model, the MDA-MB 231 cell line. The use of specific agonists and antagonists evidenced that these effects depend on the activation of the A2B receptor, which then triggers an intracellular response mediated by the adenylate cyclase/PKA/cAMP signaling pathway. Ado also increases the expression of NaV1.5 channels, a potential biomarker in breast cancer...
2016: PloS One
https://www.readbyqxmd.com/read/27911261/targeted-deletion-of-akap7-in-dentate-granule-cells-impairs-spatial-discrimination
#13
Brian W Jones, Jennifer Deem, Thomas J Younts, Michael Weisenhaus, Christina A Sanford, Margaret C Slack, Jenesa Chin, Daniela Nachmanson, Alex McKennon, Pablo E Castillo, G Stanley McKnight
Protein Kinase A (PKA) mediates synaptic plasticity and is widely implicated in learning and memory. The hippocampal dentate gyrus (DG) is thought to be responsible for processing and encoding distinct contextual associations in response to highly similar inputs. The mossy fiber (MF) axons of the dentate granule cells convey strong excitatory drive to CA3 pyramidal neurons and express presynaptic, PKA-dependent forms of plasticity. Here, we demonstrate an essential role for the PKA anchoring protein, AKAP7, in mouse MF axons and terminals...
December 2, 2016: ELife
https://www.readbyqxmd.com/read/27910854/the-genetic-basis-and-fitness-consequences-of-sperm-midpiece-size-in-deer-mice
#14
Heidi S Fisher, Emily Jacobs-Palmer, Jean-Marc Lassance, Hopi E Hoekstra
An extensive array of reproductive traits varies among species, yet the genetic mechanisms that enable divergence, often over short evolutionary timescales, remain elusive. Here we examine two sister-species of Peromyscus mice with divergent mating systems. We find that the promiscuous species produces sperm with longer midpiece than the monogamous species, and midpiece size correlates positively with competitive ability and swimming performance. Using forward genetics, we identify a gene associated with midpiece length: Prkar1a, which encodes the R1α regulatory subunit of PKA...
December 2, 2016: Nature Communications
https://www.readbyqxmd.com/read/27908835/modulation-of-signaling-through-gpcr-camp-pka-pathways-by-pde4-depends-on-stimulus-intensity-possible-implications-for-the-pathogenesis-of-acrodysostosis-without-hormone-resistance
#15
Emmanuelle Motte, Catherine Le Stunff, Claire Briet, Nicolas Dumaz, Caroline Silve
In acrodysostosis without hormone resistance, a disease caused by phosphodiesterase (PDE)-4D mutations, increased PDE activity leads to bone developmental defects but with normal renal responses to PTH. To identify potential mechanisms for these disparate responses, we compared the effect of PDE activity on hormone signaling through the GPCR-Gsα-cAMP-PKA pathway in cells from two lineages, HEK-293 cells stably overexpressing PTH1R (HEKpthr) and human dermal fibroblasts, including studies evaluating cAMP levels using an Epac-based BRET-sensor for cAMP (CAMYEL)...
November 28, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27908592/activation-of-gpr30-stimulates-gtp-binding-of-g%C3%AE-i1-protein-to-sustain-activation-of-erk1-2-in-inhibition-of-prostate-cancer-cell-growth-and-modulates-metastatic-properties
#16
Kin-Mang Lau, Fanny Man-Ting Ma, Jenny Tian Xia, Queeny Kwan Yi Chan, Chi-Fai Ng, Ka-Fai To
Previously, we reported that GPR30 activation by the receptor-specific, non-estrogenic ligand G-1 inhibited in vitro and in vivo growth of prostate cancer (PCa) cells via sustained Erk1/2 activation. Mechanism underlying the sustained Erk1/2 activation for PCa cell growth inhibition remains unclear. Here we report that G-1, through GPR30, activated Gαi1 proteins to sustain Erk1/2 activation but failed to activate adenylyl cyclase (AC) for cAMP production in PCa cells. The chemical-induced activation of AC-cAMP-PKA signaling attenuated Erk1/2 activity and blocked the cell growth inhibitory effects of G-1...
November 28, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27901058/a-kinase-anchoring-protein-4-akap4-is-an-erk1-2-substrate-and-a-switch-molecule-between-camp-pka-and-pkc-erk1-2-in-human-spermatozoa
#17
Liat Rahamim Ben-Navi, Tal Almog, Zhong Yao, Rony Seger, Zvi Naor
Mammalian spermatozoa undergo capacitation and acrosome reaction in order to fertilize the egg. The PKC-ERK1/2 pathway plays an important role in human spermatozoa motility, capacitation and the acrosome reaction. Here we demonstrate that ERK1/2 phosphorylates proAKAP4 on Thr265 in human spermatozoa in vitro and in vivo. Cyclic AMP (cAMP) had no effect on ERK1/2 activity in human spermatozoa, but stimulated the MAPK in mouse pituitary LβT2 gonadotrope cells. cAMP via PKA attenuates PKC-dependent ERK1/2 activation only in the presence of proAKAP4...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27900608/interaction-of-epac-with-non-canonical-cyclic-nucleotides
#18
Holger Rehmann
Epac1 and Epac2 are cyclic nucleotide-binding (CNB) domain containing proteins, which were originally identified as cAMP-regulated guanine nucleotide exchange factors (GEFs) for the small G-protein Rap. Therefore, Epac proteins founded next to protein kinase A (PKA) and cyclic nucleotide-regulated ion channels the third group of cAMP-responsive proteins in higher organisms. Epac proteins are involved in the regulation of several physiological processes. In particular Epac1 mediates the regulation of molecular processes underlying cell adhesion and mobility...
November 30, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27898325/determination-of-acid-dissociation-constants-pka-of-cephalosporin-antibiotics-computational-and-experimental-approaches
#19
Alyson R Ribeiro, Torsten C Schmidt
Cefapirin (CEPA) and ceftiofur (CEF) are two examples of widely used veterinarian cephalosporins presenting multiple ionization centers. However, the acid dissociation constants (pKa) of CEF are missing and experimental data about CEPA are rare. The same is true for many cephalosporins, where available data are either incomplete or even wrong. Environmentally relevant biotic and abiotic processes depend primordially on the antibiotic pH-dependent speciation. Consequently, this physicochemical parameter should be reliable, including the correct ionization center identification...
November 26, 2016: Chemosphere
https://www.readbyqxmd.com/read/27896950/ppar%C3%AE-agonists-negatively-regulate-%C3%AE-iib%C3%AE-3-integrin-outside-in-signalling-and-platelet-function-through-upregulation-of-protein-kinase-a-activity
#20
A J Unsworth, N Kriek, A P Bye, K Naran, T Sage, G D Flora, J M Gibbins
BACKGROUND: Agonists for the peroxisome proliferator activated receptor PPARγ, have been shown to have inhibitory effects on platelet activity following stimulation by GPVI and GPCR agonists. OBJECTIVES: Profound effects on thrombus formation led us to suspect a role for PPARγ agonists in the regulation of integrin αIIbβ3 mediated signalling. Both GPVI and GPCR signalling pathways lead to αIIbβ3 activation, and signalling through αIIbβ3 plays a critical role in platelet function and normal haemostasis...
November 29, 2016: Journal of Thrombosis and Haemostasis: JTH
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