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https://www.readbyqxmd.com/read/28106114/multiplexing-pka-and-erk1-2-kinases-fret-biosensors-in-living-cells-using-single-excitation-wavelength-dual-colour-flim
#1
Claire Demeautis, François Sipieter, Julien Roul, Catherine Chapuis, Sergi Padilla-Parra, Franck B Riquet, Marc Tramier
Monitoring of different signalling enzymes in a single assay using multiplex biosensing provides a multidimensional workspace to elucidate biological processes, signalling pathway crosstalk, and determine precise sequence of events at the single living cell level. In this study, we interrogate the complexity in cAMP/PKA-MAPK/ERK1&2 crosstalk by using multi-parameter biosensing experiments to correlate biochemical activities simultaneously in time and space. Using a single excitation wavelength dual colour FLIM method we are able to detect fluorescence lifetime images of two donors to simultaneously measure PKA and ERK1&2 kinase activities in the same cellular localization by using FRET biosensors...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28103136/inhibition-of-voltage-dependent-potassium-channels-mediates-camp-potentiated-insulin-secretion-in-rat-pancreatic-%C3%AE-cells
#2
Yunfeng Liu, Xiangqin Zhong, Yaqin Ding, Lele Ren, Tao Bai, Mengmeng Liu, Zhihong Liu, Yangyan Guo, Qing Guo, Yu Zhang, Jing Yang, Yi Zhang
Insulin secretion is essential for maintenance of glucose homeostasis. An important intracellular signal regulating insulin secretion is cAMP. In this report, we showed that an increase of cAMP induced by adenylyl cyclase (AC) activator forskolin or by cAMP analog db-cAMP not only potentiated insulin secretion but also inhibited Kv channels, and these effects were reversed by AC inhibitor SQ22536. The cAMP-mediated Kv channel inhibition resulted in prolongation of action potential duration, which partly accounts for the elevation of intracellular Ca(2+) induced by activation of cAMP signaling...
January 19, 2017: Islets
https://www.readbyqxmd.com/read/28076805/regulation-of-active-icam-4-on-normal-and-sickle-cell-disease-rbcs-via-akaps-is-revealed-by-afm
#3
Jing Zhang, Krithika Abiraman, Sasia-Marie Jones, George Lykotrafitis, Biree Andemariam
Human healthy (wild-type (WT)) and homozygous sickle (SS) red blood cells (RBCs) express a large number of surface receptors that mediate cell adhesion between RBCs, and between RBCs and white blood cells, platelets, and the endothelium. In sickle cell disease (SCD), abnormal adhesion of RBCs to endothelial cells is mediated by the intercellular adhesion molecule-4 (ICAM-4), which appears on the RBC membrane and binds to the endothelial αvβ3 integrin. This is a key factor in the initiation of vaso-occlusive episodes, the hallmark of SCD...
January 10, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28063130/glucocorticoids-curtail-stimuli-induced-creb-phosphorylation-in-trh-neurons-through-interaction-of-the-glucocorticoid-receptor-with-the-catalytic-subunit-of-protein-kinase-a
#4
Israim Sotelo-Rivera, Antonieta Cote-Vélez, Rosa-María Uribe, Jean-Louis Charli, Patricia Joseph-Bravo
PURPOSE: Corticosterone prevents cold-induced stimulation of thyrotropin-releasing hormone (Trh) expression in rats, and the stimulatory effect of dibutyryl cyclic-adenosine monophosphate (dB-cAMP) on Trh transcription in hypothalamic cultures. We searched for the mechanism of this interference. METHODS: Immunohistochemical analyses of phosphorylated cAMP-response element binding protein (pCREB) were performed in the paraventricular nucleus (PVN) of Wistar rats, and in cell cultures of 17-day old rat hypothalami, or neuroblastoma SH-SY5Y cells...
January 6, 2017: Endocrine
https://www.readbyqxmd.com/read/28062543/multiple-slc-and-abc-transporters-contribute-to-the-placental-transfer-of-entecavir
#5
Zhiyuan Ma, Xi Yang, Ting Jiang, Mengru Bai, Caihong Zheng, Su Zeng, Dongli Sun, Huidi Jiang
Entecavir (ETV), a nucleoside analogue with high efficacy against hepatitis B virus, is recommended as a first-line antiviral drug for the treatment of chronic hepatitis B. However, scant information is available on the use of ETV in pregnancy. To better understand the safety of ETV in pregnant women, we aimed to demonstrate whether ETV could permeate placental barrier and the underlying mechanism. Our study showed that small amount of ETV could permeate across placenta in mice. ETV accumulation in activated or non-activated BeWo cells (treated with or without forskolin) was sharply reduced in the presence of 100 μM of adenosine, cytidine and in Na+ free medium, indicating that nucleoside transporters possibly mediate the uptake of ETV...
January 6, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28057842/cyclic-amp-reverses-the-effects-of-aging-on-pacemaker-activity-and-if-in-sinoatrial-node-myocytes
#6
Emily J Sharpe, Eric D Larson, Catherine Proenza
Aerobic capacity decreases with age, in part because of an age-dependent decline in maximum heart rate (mHR) and a reduction in the intrinsic pacemaker activity of the sinoatrial node of the heart. Isolated sinoatrial node myocytes (SAMs) from aged mice have slower spontaneous action potential (AP) firing rates and a hyperpolarizing shift in the voltage dependence of activation of the "funny current," If Cyclic AMP (cAMP) is a critical modulator of both AP firing rate and If in SAMs. Here, we test the ability of endogenous and exogenous cAMP to overcome age-dependent changes in acutely isolated murine SAMs...
January 5, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28051147/%C3%AE-2-adrenoreceptor-inverse-agonist-down-regulates-muscarine-cholinergic-subtype-3-receptor-and-its-downstream-signal-pathways-in-airway-smooth-muscle-cells-in-vitro
#7
Jian Luo, Yuan-Hua Liu, Wei Luo, Zhu Luo, Chun-Tao Liu
Mechanisms underlying β2-adrenoreceptor (β2AR) inverse agonist mediated bronchoprotectiveness remain unknown. We incubated ICI118,551, formoterol, budesonide, and formoterol plus budesonide, as well as ICI118,551 or pindolol plus formoterol, ICI118,551 plus forskolin, SQ22,536 or H89 plus formoterol in ASMCs to detect expressions of M3R, PLCβ1 and IP3. The level of M3R in the presence of 10(-5) mmol/L ICI118,551 were significantly decreased at 12 h, 24 h and 48 h (P < 0.05), and at 24 h were significantly reduced in ICI118,551 with concentration of 10(-5 )mmol/L, 10(-6 )mmol/L, 10(-7 )mmol/L, and 10(-8 )mmol/L (P < 0...
January 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28049031/the-efficacy-of-dynorphin-fragments-at-the-%C3%AE%C2%BA-%C3%AE-and-%C3%AE-opioid-receptor-in-transfected-hek-cells-and-in-an-animal-model-of-unilateral-peripheral-inflammation
#8
M Morgan, A Heffernan, F Benhabib, S Wagner, A K Hewavitharana, P N Shaw, P J Cabot
Dynorphin 1-17 is an endogenous peptide that is released at sites of inflammation by leukocytes, binding preferentially to κ-opioid receptors (KOP) to mediate nociception. We have previously shown that dynorphin 1-17 is rapidly biotransformed to smaller peptide fragments in inflamed tissue homogenate. This study aimed to determine the efficacy and potency of selected dynorphin fragments produced in an inflamed environment at the KOP, μ and δ-opioid receptors (MOP and DOP respectively) and in a model of inflammatory pain...
December 31, 2016: Peptides
https://www.readbyqxmd.com/read/28002566/camp-stimulates-transepithelial-short-circuit-current-and-fluid-transport-across-porcine-ciliary-epithelium
#9
Angela King-Wah Cheng, Mortimer M Civan, Chi-Ho To, Chi-Wai Do
Purpose: To investigate the effects of cAMP on transepithelial electrical parameters and fluid transport across porcine ciliary epithelium. Methods: Transepithelial electrical parameters were determined by mounting freshly isolated porcine ciliary epithelium in a modified Ussing chamber. Similarly, fluid movement across intact ciliary body was measured with a custom-made fluid flow chamber. Results: Addition of 1, 10, and 100 μM 8-Br-cAMP (cAMP) to the aqueous side (nonpigmented ciliary epithelium, NPE) induced a sustained increase in short-circuit current (Isc)...
December 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27995573/forskolin-induces-hyperphosphorylation-of-tau-accompanied-by-cell-cycle-reactivation-in-primary-hippocampal-neurons
#10
Hai-Hong Wang, Yan Li, Ang Li, Fang Yan, Zhen-Lin Li, Zhong-Ying Liu, Lei Zhang, Jian Zhang, Wei-Ren Dong, Lin Zhang
Abnormally hyperphosphorylated tau is the major protein constituent of neurofibrillary tangles (NFTs) in the brain of Alzheimer disease (AD) patients. Cell cycle reactivation is considered an important neuropathological feature of AD, and re-expression and activation of cell cycle regulators are known to occur in neurons containing NFTs. The aim of the present study was to investigate cell cycle reactivation during tau hyperphosphorylation in primary hippocampal neurons. We used forskolin, a specific activator of PKA, to induce tau hyperphosphorylation in cultured primary hippocampal neurons, and then measured levels of cyclin D1 and cyclin B1...
December 19, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27967235/17%C3%AE-hsd-type-12-like-is-responsible-for-maturation-inducing-hormone-synthesis-during-oocyte-maturation-in-masu-salmon
#11
Shigeho Ijiri, Yasushi Shibata, Nonoha Takezawa, Yukinori Kazeto, Naoki Takatsuka, Erika Kato, Seishi Hagihara, Yuichi Ozaki, Shinji Adachi, Kohei Yamauchi, Yoshitaka Nagahama
The maturation-inducing hormone 17α,20β-dihydroxy-4-pregnen-3-one (DHP) was first identified in the amago salmon. However, although carbonyl reductase-like 20β-hydroxysteroid dehydrogenase (CR/20β-HSD) was reported to convert 17α-hydroxyprogesterone (17OHP) to DHP in rainbow trout, we previously found that CR/20β-HSD mRNA was not up-regulated in stimulated granulosa cells from masu salmon, which suggested that DHP is synthesized by a different enzyme. Accordingly, the present study aimed to identify the specific 20β-hydroxysteroid dehydrogenase (20β-HSD) responsible for DHP production by granulosa cells during final oocyte maturation in masu salmon...
December 14, 2016: Endocrinology
https://www.readbyqxmd.com/read/27942503/rapid-induction-of-neural-differentiation-in-human-umbilical-cord-matrix-mesenchymal-stem-cells-by-camp-elevating-agents
#12
Atefeh Shahbazi, Majid Safa, Fatemeh Alikarami, Saeid Kargozar, Mohammad Hossein Asadi, Mohammad Taghi Joghataei, Mansoureh Soleimani
Human umbilical cord matrix (hUCM) is considered as a promising source of mesenchymal stem cells (MSCs) due to several advantages over other tissues. The potential of neural differentiation of hUCM-MSCs is of great interest in the context of treating neurodegenerative diseases. In recent years, considerable efforts have been made to establish in vitro conditions for improving the differentiation of hUCM-MSCs toward neuronal cells. In the present study, we evaluated the neural differentiation potential of hUCM-MSCs in the presence of cAMP-elevating agents forskolin and 3-isobutyl-1-methylxanthine (IBMX)...
2016: International Journal of Molecular and Cellular Medicine
https://www.readbyqxmd.com/read/27941075/%C3%AE-%C3%AE-%C3%AE-enac-is-inhibited-by-cftr-but-stimulated-by-camp-in-xenopus-laevis-oocytes
#13
Robert Rauh, Christian Hoerner, Christoph Korbmacher
The epithelial sodium channel (ENaC) and the CFTR chloride channel critically regulate airway surface liquid by driving fluid absorption and secretion, respectively. Their functional interplay is complex and incompletely understood. ENaC is a heteromeric channel with three well characterised subunits (α, β, γ). In humans, an additional δENaC subunit exists in lung and several other tissues where it may replace the α-subunit to form δβγENaC. Little is known about the physiological role of δβγENaC and its possible interaction with CFTR...
December 9, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27935256/pigment-translocation-in-caridean-shrimp-chromatophores-receptor-type-signal-transduction-second-messengers-and-cross-talk-among-multiple-signaling-cascades
#14
Sarah Ribeiro Milograna, Márcia Regina Ribeiro, Fernanda Tinti Bell, John Campbell McNamara
Pigment aggregation in shrimp chromatophores is triggered by red pigment concentrating hormone (RPCH), a neurosecretory peptide whose plasma membrane receptor may be a G-protein coupled receptor (GPCR). While RPCH binding activates the Ca(2+) /cGMP signaling cascades, a role for cyclic AMP (cAMP) in pigment aggregation is obscure, as are the steps governing Ca(2+) release from the smooth endoplasmic reticulum (SER). A role for the antagonistic neuropeptide, pigment dispersing homone (α-PDH) is also unclear...
November 2016: Journal of Experimental Zoology. Part A, Ecological Genetics and Physiology
https://www.readbyqxmd.com/read/27930744/interactions-of-calcium-fluctuations-during-cardiomyocyte-contraction-with-real-time-camp-dynamics-detected-by-fret
#15
Julia U Sprenger, Nadja I Bork, Jonas Herting, Thomas H Fischer, Viacheslav O Nikolaev
Calcium (Ca2+) and 3',5'-cyclic adenosine monophosphate (cAMP) play a critical role for cardiac excitation-contraction-coupling. Both second messengers are known to interact with each other, for example via Ca2+-dependent modulation of phosphodiesterase 1 (PDE1) and adenylyl cyclase 5/6 (AC 5/6) activities, which is supposed to occur especially at the local level in distinct subcellular microdomains. Currently, many studies analyze global and local cAMP signaling and its regulation in resting cardiomyocytes devoid of electrical stimulation...
2016: PloS One
https://www.readbyqxmd.com/read/27922115/perilipin-5-fine-tunes-lipid-oxidation-to-metabolic-demand-and-protects-against-lipotoxicity-in-skeletal-muscle
#16
Claire Laurens, Virginie Bourlier, Aline Mairal, Katie Louche, Pierre-Marie Badin, Etienne Mouisel, Alexandra Montagner, André Marette, Angelo Tremblay, John S Weisnagel, Hervé Guillou, Dominique Langin, Denis R Joanisse, Cedric Moro
Lipid droplets (LD) play a central role in lipid homeostasis by controlling transient fatty acid (FA) storage and release from triacylglycerols stores, while preventing high levels of cellular toxic lipids. This crucial function in oxidative tissues is altered in obesity and type 2 diabetes. Perilipin 5 (PLIN5) is a LD protein whose mechanistic and causal link with lipotoxicity and insulin resistance has raised controversies. We investigated here the physiological role of PLIN5 in skeletal muscle upon various metabolic challenges...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27904475/transforming-growth-factor-beta-1-a-cytokine-with-regenerative-functions
#17
REVIEW
Wale Sulaiman, Doan H Nguyen
We review the biology and role of transforming growth factor beta 1 (TGF-β1) in peripheral nerve injury and regeneration, as it relates to injuries to large nerve trunks (i.e., sciatic nerve, brachial plexus), which often leads to suboptimal functional recovery. Experimental studies have suggested that the reason for the lack of functional recovery resides in the lack of sufficient mature axons reaching their targets, which is a result of the loss of the growth-supportive environment provided by the Schwann cells in the distal stump of injured nerves...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27901486/triple-negative-breast-cancer-development-can-be-selectively-suppressed-by-sustaining-an-elevated-level-of-cellular-cyclic-amp-through-simultaneously-blocking-its-efflux-and-decomposition
#18
Wei Wang, Yue Li, Jessica Y Zhu, Dongdong Fang, Han-Fei Ding, Zheng Dong, Qing Jing, Shi-Bing Su, Shuang Huang
Triple negative breast cancer (TNBC) has the highest mortality among all breast cancer types and lack of targeted therapy is a key factor contributing to its high mortality rate. In this study, we show that 8-bromo-cAMP, a cyclic adenosine monophosphate (cAMP) analog at high concentration (> 1 mM) selectively suppresses TNBC cell growth. However, commonly-used cAMP-elevating agents such as adenylyl cyclase activator forskolin and pan phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) are ineffective...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27894809/cyclic-amp-camp-confers-drug-resistance-against-dna-damaging-agents-via-pkaia-in-cml-cells
#19
Ling-Yi Xiao, Wai-Ming Kan
Cyclic adenosine monophosphate (cAMP) regulates many vital functions such as metabolism, proliferation, differentiation and death. Depending on cell types and stimulators, cAMP could either promote or attenuate cell death. cAMP signal can be transduced by protein kinase A (PKA) and/or exchange protein directly activated by cAMP (EPAC). In CML cells, cAMP may suppress their proliferation and enhance their differentiation. However, the role of cAMP on DNA damaging agent toxicity and the mechanism involved has not been studied...
January 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27891679/adenylyl-cyclase-3-adenylyl-cyclase-associated-protein-1-cap1-complex-mediates-the-anti-migratory-effect-of-forskolin-in-pancreatic-cancer-cells
#20
Sierra N Quinn, Sarai H Graves, Clayton Dains-McGahee, Emilee M Friedman, Humma Hassan, Piotr Witkowski, Maria E Sabbatini
Pancreatic cancer is one of the most lethal human malignancies. A better understanding of the intracellular mechanism of migration and invasion is urgently needed to develop treatment that will suppress metastases and improve overall survival. Cyclic adenosine monophosphate (cyclic AMP) is a second messenger that has shown to regulate migration and invasion of pancreatic cancer cells. The rise of cyclic AMP suppressed migration and invasion of pancreatic ductal adenocarcinoma cells. Cyclic AMP is formed from cytosolic ATP by the enzyme adenylyl cyclase (AC)...
November 27, 2016: Molecular Carcinogenesis
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