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https://www.readbyqxmd.com/read/28453888/live-imaging-of-extracellular-signal-regulated-kinase-and-protein-kinase-a-activities-during-thrombus-formation-in-mice-expressing-biosensors-based-on-f%C3%A3-rster-resonance-energy-transfer
#1
Takuya Hiratsuka, Takeshi Sano, Hisashi Kato, Naoki Komatsu, Masamichi Imajo, Yuji Kamioka, Kenta Sumiyama, Fumiaki Banno, Toshiyuki Miyata, Michiyuki Matsuda
BACKGROUND: Dynamic features of thrombus formation have been visualized by conventional video wide field microscopy or confocal microscopy in live mouse. However, due to technical limitations precise spatiotemporal regulation of intracellular signaling molecule activities, which have been extensively studied in vitro, remains elusive in vivo. OBJECTIVES: By two-photon excitation microscopy of transgenic mice expressing Förster resonance energy transfer (FRET) biosensors for extracellular signal-regulated kinase (ERK) and protein kinase A (PKA), we visualized ERK and PKA activities during thrombus formation in laser-injured subcutaneous arterioles RESULTS: When a core of densely packed platelets was developed, ERK activity was increased from the basal region close to the injured arterioles...
April 28, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28448991/participation-of-antidiuretic-hormone-adh-in-asthma-exacerbations-induced-by-psychological-stress-via-pka-pkc-signal-pathway-in-airway-related-vagal-preganglionic-neurons-avpns
#2
Lili Hou, Lei Zhu, Min Zhang, Xingyi Zhang, Guoqing Zhang, Zhenwei Liu, Qiang Li, Xin Zhou
AIMS: Present study was performed to examine whether ADH was implicated in psychological stress asthma and to explore the underlying molecular mechanism. METHODS: We not only examined ADH levels in the cerebrospinal fluid (CSF) via radioimmunoassay, but also measured ADH receptor (ADHR) expression in airway-related vagal preganglionic neurons (AVPNs) through real-time PCR in all experimental mice. Western blotting was performed to evaluate the relationship between ADH and PKA/PKC in psychological stress asthma...
April 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28448042/imaging-the-neutrophil-phagosome-and-cytoplasm-using-a-ratiometric-ph-indicator
#3
Juliet R Foote, Adam P Levine, Philippe Behe, Michael R Duchen, Anthony W Segal
Neutrophils are crucial to host innate defense and, consequently, constitute an important area of medical research. The phagosome, the intracellular compartment where the killing and digestion of engulfed particles take place, is the main arena for neutrophil pathogen killing that requires tight regulation. Phagosomal pH is one aspect that is carefully controlled, in turn regulating antimicrobial protease activity. Many fluorescent pH-sensitive dyes have been used to visualize the phagosomal environment. S-1 has several advantages over other pH-sensitive dyes, including its dual emission spectra, its resistance to photo-bleaching, and its high pKa...
April 5, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28446817/shh-mediated-centrosomal-recruitment-of-pka-promotes-symmetric-proliferative-neuroepithelial-cell%C3%A2-division
#4
Murielle Saade, Elena Gonzalez-Gobartt, Rene Escalona, Susana Usieto, Elisa Martí
Tight control of the balance between self-expanding symmetric and self-renewing asymmetric neural progenitor divisions is crucial to regulate the number of cells in the developing central nervous system. We recently demonstrated that Sonic hedgehog (Shh) signalling is required for the expansion of motor neuron progenitors by maintaining symmetric divisions. Here we show that activation of Shh/Gli signalling in dividing neuroepithelial cells controls the symmetric recruitment of PKA to the centrosomes that nucleate the mitotic spindle, maintaining symmetric proliferative divisions...
April 27, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28444510/starvation-signals-in-yeast-are-integrated-to-coordinate-metabolic-reprogramming-and-stress-response-to-ensure-longevity
#5
REVIEW
Nianshu Zhang, Lu Cao
Studies on replicative and chronological aging in Saccharomyces cerevisiae have greatly advanced our understanding of how longevity is regulated in all eukaryotes. Chronological lifespan (CLS) of yeast is defined as the age-dependent viability of non-dividing cell populations. A number of nutrient sensing and signal transduction pathways (mainly TOR and PKA) have been shown to regulate CLS, yet it is poorly understood how the starvation signals transduced via these pathways lead to CLS extension. Using reporters whose expressions are induced by glucose starvation, we have screened the majority of the 'signaling' mutants in the yeast genome and identified many genes that are necessary for stress response...
April 25, 2017: Current Genetics
https://www.readbyqxmd.com/read/28443887/metal-ion-induced-supramolecular-pka-tuning-and-fluorescence-regeneration-of-a-p-sulfonatocalixarene-encapsulated-neutral-red-dye
#6
M N Shinde, R Khurana, N Barooah, A C Bhasikuttan, J Mohanty
The host-guest interactions and the consequent modulation in the prototropic equilibrium of a phenazine dye, neutral red, with p-sulfonatocalix[4]arene (SCX4) and p-sulfonatocalix[6]arene (SCX6) macrocyclic hosts have been investigated. Both the neutral (NR) and cationic (NRH(+)) forms of dyes formed inclusion complexes with SCX6, with a larger binding constant for the latter (K = 8.6 × 10(5) M(-1)versus 4.8 × 10(3) M(-1)) due to the cation receptor behavior of the calixarenes. The distinct differences in the binding constant of NR and NRH(+) provided a finite tuning of pKa between 6...
April 26, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28443065/hemoglobin-improved-protection-in-cultured-cerebral-cortical-astroglial-cells-inhibition-of-oxidative-stress-and-caspase-activation
#7
Fatma Amri, Ikram Ghouili, Marie-Christine Tonon, Mohamed Amri, Olfa Masmoudi-Kouki
Oxidative stress plays a major role in triggering astroglial cell death in diverse neuropathological conditions such as ischemia and neurodegenerative diseases. Numerous studies indicate that hemoglobin (Hb) is expressed in both resting and reactive glia cells, but nothing is known regarding a possible role of Hb on astroglial cell survival. Thus, the purpose of the present study was to investigate the potential glioprotective effect of Hb on hydrogen peroxide (H2O2)-induced oxidative stress and apoptosis in cultured rat astrocytes...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28442264/mitochondrial-lon-protease-dependent-degradation-of-cytochrome-c-oxidase-subunits-under-hypoxia-and-myocardial-ischemia
#8
Naresh B V Sepuri, Rajesh Angireddy, Satish Srinivasan, Manti Guha, Joseph Spear, Bin Lu, Hindupur K Anandatheerthavarada, Carolyn K Suzuki, Narayan G Avadhani
The mitochondrial ATP dependent matrix protease, Lon, is involved in the maintenance of mitochondrial DNA nucleoids and degradation of abnormal or misfolded proteins. The Lon protease regulates mitochondrial Tfam (mitochondrial transcription factor A) level and thus modulates mitochondrial DNA (mtDNA) content. We have previously shown that hypoxic stress induces the PKA-dependent phosphorylation of cytochrome c oxidase (CcO) subunits I, IVi1, and Vb and a time-dependent reduction of these subunits in RAW 264...
April 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28442261/identification-of-a-novel-fluoropyrrole-derivative-as-a-potassium-competitive-acid-blocker-with-long-duration-of-action
#9
Haruyuki Nishida, Yasuyoshi Arikawa, Keizo Hirase, Toshihiro Imaeda, Nobuhiro Inatomi, Yasunobu Hori, Jun Matsukawa, Yasushi Fujioka, Teruki Hamada, Motoo Iida, Mitsuyoshi Nishitani, Akio Imanishi, Hideo Fukui, Fumio Itoh, Masahiro Kajino
With the aim to find a novel long-lasting potassium-competitive acid blocker (P-CAB) that would perfectly overcome the limitations of proton pump inhibitors (PPIs), we tried various approaches based on pyrrole derivative 1b as a lead compound. As part of a comprehensive approach to identification of a new drug, we explored excellent compounds that have low lipophilicity by introducing a polar hetero-aromatic group at position 5 of the pyrrole ring. Among the compounds synthesized, fluoropyrrole derivative 37c, which has a 2-F-3-Py group at the fifth position, lower pKa, and much lower ClogP and logD values than 1b dose, showed potent gastric-acid suppressive action resulting from gastric H(+),K(+)-ATPase inhibition in animal models...
April 13, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28441017/equilibration-of-micelle-polyelectrolyte-complexes-mechanistic-differences-between-static-and-annealed-charge-distributions
#10
Jennifer E Laaser, Michael McGovern, Yaming Jiang, Elise Lohmann, Theresa M Reineke, David C Morse, Kevin D Dorfman, Timothy P Lodge
The role of charge density and charge annealing in polyelectrolyte complexation was investigated through systematic comparison of two micelle-polyelectrolyte systems. First, poly(dimethylaminoethyl methacrylate)-block-poly(styrene) (PDMAEMA-b-PS) micelles were complexed with poly(styrenesulfonate) (PSS) at pH values above and below the pKa of PDMAEMA to investigate the role of charge annealing in the complexation process. Second, complexes of poly(DMAEMA-stat-oligo(ethylene glycol) methyl ether methacrylate)-block-poly(styrene) (P(DMAEMA-stat-OEGMA)-b-PS) micelles with the same PSS at low pH were used to investigate how the complexation process differs when the charged sites are in fixed positions along the polymer chains...
April 25, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28438669/the-effects-of-chinese-medicines-on-camp-pka-signaling-pathway-in-central-nervous-system-dysfunction
#11
REVIEW
Lin Li, Xiang Fan, Xi-Ting Zhang, Shao-Qian Yue, Zuo-Yan Sun, Jin-Qiang Zhu, Jun-Hua Zhang, Xiu-Mei Gao, Han Zhang
Neuropathological injury in adult mammal central nervous system (CNS) may cause axon disruption, neuronal death and produce lasting neurological deficits. Failure of axon regeneration is one of the major challenges for CNS function recovery. Recently, cAMP/PKA signaling pathway has been proven to be a critical regulator for neuronal regeneration, neuroplasticity and learning and memory ability. And previous studies have revealed the effects of Chinese medicines on prevention and treatment of CNS dysfunction medicated by cAMP/PKA signaling pathway partially...
April 21, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28438657/the-thiol-of-human-serum-albumin-acidity-microenvironment-and-mechanistic-insights-on-its-oxidation-to-sulfenic-acid
#12
Jenner Bonanata, Lucía Turell, Laura Antmann, Gerardo Ferrer-Sueta, Santiago Botasini, Eduardo Méndez, Beatriz Alvarez, E Laura Coitiño
Human serum albumin (HSA) has a single reduced cysteine residue, Cys34, whose acidity has been controversial. Three experimental approaches (pH-dependence of reactivity towards hydrogen peroxide, ultraviolet titration and infrared spectroscopy) are used to determine that the pKa value in delipidated HSA is 8.1 ± 0.2 at 37°C and 0.1M ionic strength. Molecular dynamics simulations of HSA in the sub-microsecond timescale show that while sulfur exposure to solvent is limited and fluctuating in the thiol form, it increases in the thiolate, stabilized by a persistent hydrogen-bond (HB) network involving Tyr84 and bridging waters to Asp38 and Gln33 backbone...
April 21, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28437476/clc-3-chloride-channel-mediates-the-role-of-parathyroid-hormone-1-34-on-osteogenic-differentiation-of-osteoblasts
#13
Xiaolin Lu, Yin Ding, Qiannan Niu, Shijie Xuan, Yan Yang, Yulong Jin, Huan Wang
INTRODUCTION: Different concentrations of parathyroid hormone [1-34] (PTH [1-34]) can have totally opposite effects on osteoblasts. Intermittent stimulation with PTH can significantly increase bone mineral density in vitro, mainly through the protein kinase A (PKA) signaling pathway, which phosphorylates runt-related transcription factor 2 (Runx2). The ClC-3 chloride channel, an important anion channel, can also promote osteogenesis via the Runx2 pathway based on recent studies. The purpose of our study, therefore, is to research whether the ClC-3 chloride channel has an effect on PTH osteodifferentiation in MC3T3-E1 cells...
2017: PloS One
https://www.readbyqxmd.com/read/28435972/-glp-1-gip-gcg-receptor-triagonist-improves-the-cognitive-behaviors-in-triple-transgenic-mice-of-alzheimer-s-disease
#14
Juan-Juan Jiao, Christian Hölscher, Tian Li, Xue-Fan Dong, Xue-Song Qu, Yue Cao, Mei-Na Wu, Zhao-Jun Wang, Jin-Shun Qi
Alzheimer's disease (AD) is a progressively neurodegenerative disorder, which seriously affects human health but is still irreversible up to now. Recent studies indicate that type 2 diabetes mellitus (T2DM) is an important risk factor for AD, and the drugs used for treatment of T2DM have shown some neuroprotective effects in the treatment of AD. Glucagon-like peptide-1 (GLP-1)/ glucose-dependent insulinotropic polypeptide (GIP)/glucagon (Gcg) receptor Triagonist is a new monomeric polypeptide equally activating the GLP-1/GIP/Gcg receptors, which is built on the basis of GLP-1/Gcg receptor coagonist core sequence, and incorporated with partial amino acids of GIP...
April 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28433631/detection-of-camp-and-of-pka-activity-in-saccharomyces-cerevisiae-single-cells-using-fluorescence-resonance-energy-transfer-fret-probes
#15
Sonia Colombo, Serena Broggi, Maddalena Collini, Laura D'Alfonso, Giuseppe Chirico, Enzo Martegani
In Saccharomyces cerevisiae the second messenger cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) play a central role in metabolism regulation, stress resistance and cell cycle progression. To monitor cAMP levels and PKA activity in vivo in single S. cerevisiae cells, we expressed an Epac-based FRET probe and a FRET-based A-kinase activity reporter, which were proven to be useful live-cell biosensors for cAMP levels and PKA activity in mammalian cells. Regarding detection of cAMP in single yeast cells, we show that in wild type strains the CFP/YFP fluorescence ratio increased immediately after glucose addition to derepressed cells, while no changes were observed when glucose was added to a strain that is not able to produce cAMP...
April 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28432305/systematic-synergy-of-glucose-and-glp-1-to-stimulate-insulin-secretion-revealed-by-quantitative-phosphoproteomics
#16
Jia-Shu Tang, Qing-Run Li, Jia-Ming Li, Jia-Rui Wu, Rong Zeng
GLP-1 synergizes with glucose in regulating pancreatic β-cell function, including facilitating β-cell survival and insulin secretion. Though it has been widely accepted that phosphorylation is extremely important in regulating β-cell functions, our knowledge to the global mechanism is still limited. Here we performed a quantitative phosphoproteomics study to systematically present the synergistic regulation of INS-1E cell phosphoproteome mediated by glucose and GLP-1. We generated the largest pancreatic β-cell phosphoproteome by identifying 25,327 accurately localized phosphorylation sites on 5,389 proteins...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28431968/cannabinoid-cb1-and-cb2-receptors-differentially-modulate-l-and-t-type-ca-2-channels-in-rat-retinal-ganglion-cells
#17
Wen-Jing Qian, Ning Yin, Feng Gao, Yanying Miao, Qian Li, Fang Li, Xing-Huai Sun, Xiong-Li Yang, Zhongfeng Wang
Endocannabinoid signaling system is involved in regulating multiple neuronal functions in the central nervous system by activating G-protein coupled cannabinoid CB1 and CB2 receptors (CB1Rs and CB2Rs). Growing evidence has shown that CB1Rs and CB2Rs are extensively expressed in retinal ganglion cells (RGCs). Here, modulation of L- and T-types Ca(2+) channels by activating CB1Rs and CB2Rs in RGCs was investigated. Triple immunofluorescent staining showed that L-type subunit CaV1.2 was co-localized with T-type subunits (CaV3...
April 18, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28431778/olmesartan
#18
Abdulrahman A Al-Majed, Ahmed H H Bakheit, Hatem A Abdel Aziz, Abdulelah A M Al-Jallal
Olmesartan is an angiotensin receptor blockers with actions similar to those of losartan; it is used for the treatment of high blood pressure by relaxing blood vessels for this reason blood can flow more easily. It could be used alone or in combination with other antihypertensive drugs. This chapter gives a comprehensive profile of olmesartan, containing detailed nomenclature, formulae, elemental analysis, and appearance of the drug. In addition this chapter also describes several methods of synthesis and usage of the olmesartan...
2017: Profiles of Drug Substances, Excipients, and related Methodology
https://www.readbyqxmd.com/read/28430917/pka-differentially-regulates-adipose-depots-to-control-energy-expenditure
#19
Barton Wicksteed, Lorna M Dickson
No abstract text is available yet for this article.
March 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28430864/the-gnih-lpxrfa-system-s-regulation-of-reproduction-in-the-brain-pituitary-axis-of-the-zebrafish-danio-rerio
#20
Olivia Smith Spicer, Nilli Zmora, Ten-Tsao Wong, Matan Golan, Berta Levavi-Sivan, Yoav Gothilf, Yonathan Zohar
Gonadotropin-inhibitory hormone (GNIH) was discovered in quail with the ability to reduce gonadotropin expression/secretion in the pituitary. There have been few studies on GNIH orthologs in teleosts (Lpxrfa peptides), which have provided inconsistent results. Therefore, the goal of this study was to determine the roles and modes of action by which Lpxrfa exerts its functions in the brain-pituitary axis of zebrafish (Danio rerio). We localized Lpxrfa soma to the ventral hypothalamus, with fibers extending throughout the brain and to the pituitary...
April 18, 2017: Biology of Reproduction
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