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https://www.readbyqxmd.com/read/28107550/enhanced-trpc-channel-mediated-ca-2-influx-in-the-cells-with-phospholipase-c-%C3%AE-1-overexpression-its-possible-role-in-coronary-artery-spasm
#1
Kazuo Murakami, Tomohiro Osanai, Makoto Tanaka, Kimitaka Nishizaki, Takahiko Kinjo, Tomohiro Tanno, Yuji Ishida, Akiko Suzuki, Tomohide Endo, Hirofumi Tomita, Ken Okumura
We reported that coronary spasm was induced in the transgenic mice with the increased phospholipase C (PLC)-δ1 activity. We investigated the effect of enhanced PLC-δ1 on Ca(2+) influx and its underlying mechanisms. We used human embryonic kidney (HEK)-293 and coronary arteries-smooth-muscle cells (CASMC). Intracellular free Ca(2+) concentration ([Ca(2+) ]i ) (nM) was measured by fura-2, and Ca(2+) influx was evaluated by the increase in [Ca(2+) ]i after addition of extracellular Ca(2+) . Acetylcholine (ACh) was used to induce Ca(2+) influx...
January 20, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28106831/ablation-of-protein-kinase-ck2%C3%AE-in-skeletal-muscle-fibers-interferes-with-their-oxidative-capacity
#2
Nane Eiber, Luca Simeone, Said Hashemolhosseini
The tetrameric protein kinase CK2 was identified playing a role at neuromuscular junctions by studying CK2β-deficient muscle fibers in mice, and in cultured immortalized C2C12 muscle cells after individual knockdown of CK2α and CK2β subunits. In muscle cells, CK2 activity appeared to be at least required for regular aggregation of nicotinic acetylcholine receptors, which serves as a hallmark for the presence of a postsynaptic apparatus. Here, we set out to determine whether any other feature accompanies CK2β-deficient muscle fibers...
January 19, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28106663/the-role-of-laser-doppler-flowmetry-tests-serum-angiopoietin-2-asymmetric-and-symmetric-dimethylarginine-to-predict-outcome-in-chronic-kidney-disease
#3
János Nemcsik, Orsolya Cseprekál, József Egresits, Jan Kielstein, Philipp Kümpers, Alexander Lukasz, Ádám Tabák, Adrienn Marton, Zsófia K Németh, Zoltán Járai, Gabriella Godina, László Sallai, Katalin Farkas, István Kiss, András Tislér
OBJECTIVE: The role of biochemical and functional markers of microvascular dysfunction to predict cardiovascular outcomes in nondialyzed chronic kidney disease (CKD) remains unclear. In this prospective cohort study, we assessed whether biochemical [serum level of angiopoietin-2 (Ang-2), asymmetric and symmetric dimethylarginin] and functional (laser Doppler flowmetry) measures of microvascular function predicted cardiovascular events, cardiovascular and all-cause mortality in CKD patients...
January 18, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28106547/phenotype-dependent-interactions-between-n-acetyl-l-aspartate-and-acetyl-coa-in-septal-sn56-cholinergic-cells-exposed-to-an-excess-of-zinc
#4
Marlena Zyśk, Hanna Bielarczyk, Sylwia Gul-Hinc, Aleksandra Dyś, Beata Gapys, Anna Ronowska, Monika Sakowicz-Burkiewicz, Andrzej Szutowicz
Pyruvate dehydrogenase reaction utilizing glucose-derived pyruvate is an almost exclusive source of acetyl-CoA in different cell mitochondrial compartments of the brain. In neuronal mitochondria, the largest fraction of acetyl-CoA is utilized for energy production and the much smaller one for N-acetyl-L-aspartate (NAA) synthesis. Cholinergic neurons, unlike others, require additional amounts of acetyl-CoA for acetylcholine synthesis. Therefore, several neurotoxic signals, which inhibit pyruvate dehydrogenase, generate deeper shortages of acetyl-CoA and greater mortality of cholinergic neurons than noncholinergic ones...
January 20, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28106328/on-the-influence-of-the-protonation-states-of-active-site-residues-on-ache-reactivation-a-qm-mm-approach
#5
Thomas Driant, Florian Nachon, Cyril Ollivier, Pierre-Yves Renard, Etienne Derat
Acetylcholinesterase (AChE) is an enzyme of the serine hydrolase superfamily and a mediator of the signal transmission at cholinergic synapses catalysing acetylcholine cleavage into an acetate and a choline. This enzyme is vulnerable to covalent inhibition by organophosphate compounds (like VX). The covalent inhibition of AChE does not revert spontaneously and in order to restore catalytic activity known reactivator compounds have limited action. Simulations of VX-inhibited AChE reactivation by pralidoxime, a classical reactivator, were performed by QM/MM...
January 19, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28106317/changes-in-vascular-reactivity-and-endothelial-ca-2-dynamics-with-chronic-low-flow
#6
Mark S Taylor, Chung-Sik Choi, Leith Bayazid, Katherine E Glosemeyer, Calvin C P Baker, David S Weber
Disruption of blood flow promotes endothelial dysfunction and predisposes vessels to remodeling and atherosclerosis. Recent findings suggest spatial and temporal tuning of local Ca(2+) signals along the endothelium is vital to vascular function. In the current study, we examined whether chronic flow disruption causes alteration of dynamic endothelial Ca(2+) signal patterning associated with changes in vascular structure and function. For these studies, we performed surgical partial-ligation (PL) of the left carotid arteries of mice to establish chronic low flow for 2 weeks; right carotid arteries remained open and served as controls (C)...
January 20, 2017: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/28105289/development-of-4-heteroarylamino-1-azaspiro-oxazole-5-3-bicyclo-2-2-2-octanes-as-%C3%AE-7-nicotinic-receptor-agonists
#7
Matthew D Hill, Haiquan Fang, H Dalton King, Christiana I Iwuagwu, Ivar M McDonald, James Cook, F Christopher Zusi, Robert A Mate, Ronald J Knox, Debra Post-Munson, Amy Easton, Regina Miller, Kimberley Lentz, Wendy Clarke, Yulia Benitex, Nicholas Lodge, Robert Zaczek, Rex Denton, Daniel Morgan, Linda Bristow, John E Macor, Richard Olson
We describe the synthesis of quinuclidine-containing spiroimidates and their utility as α7 nicotinic acetylcholine receptor (nAChR) partial agonists. A convergent synthetic route allowed for rapid SAR investigation and provided a diverse set of fused 6,5-heteroaryl analogs. Two potent and selective α7 nAChR partial agonists, (1'S,3'R,4'S)-N-(7-bromopyrrolo[2,1-f][1,2,4]triazin-4-yl)-4H-1'-azaspiro[oxazole-5,3'-bicyclo[2.2.2]octan]-2-amine (20) and (1'S,3'R,4'S)-N-(7-chloropyrrolo[2,1-f][1,2,4]triazin-4-yl)-4H-1'-azaspiro[oxazole-5,3'-bicyclo[2...
January 12, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28103719/pegylated-nanoliposomal-clusterin-for-amyloidogenic-light-chain-induced-endothelial-dysfunction
#8
Diana Guzman-Villanueva, Raymond Q Migrino, Seth Truran, Nina Karamanova, Daniel A Franco, Camelia Burciu, Subhadip Senapati, Dobrin Nedelkov, Parameswaran Hari, Volkmar Weissig
Light chain (AL) amyloidosis is a disease associated with significant morbidity and mortality arising from multi-organ injury induced by amyloidogenic light chain proteins (LC). There is no available treatment to reverse the toxicity of LC. We previously showed that chaperone glycoprotein clusterin (CLU) and nanoliposomes (NL), separately, restore human microvascular endothelial function impaired by LC. In this work, we aim to prepare PEGylated-nanoliposomal clusterin (NL-CLU) formulations that could allow combined benefit against LC while potentially enabling efficient delivery to microvascular tissue, and test efficacy on human arteriole endothelial function...
January 20, 2017: Journal of Liposome Research
https://www.readbyqxmd.com/read/28102743/expression-and-alteration-of-bkca-channels-in-the-sphincter-of-oddi-s-from-rabbits-with-hypercholesterolemia
#9
Dan Feng, Haiyan Nan, Wen Wang, Linfeng Yan, Pang Du, Lin Zuo, Kun Zhang, Minggao Zhao, Guangbin Cui
This study aimed to investigate the expression and function of BKCa channels in the Sphincter of Oddi (SO) in a rabbit model of hypercholesterolemia (HC). New Zealand white rabbits were randomly divided into two groups: the control group was fed standard chow (n = 18) whereas the high-cholesterol group was fed cholesterol-enriched chow containing 1.5% cholesterol (n = 18). The serum cholesterol level was significantly greater in the HC groups than in the control group, but there was no significant difference in body weight between the control and HC groups...
January 19, 2017: Channels
https://www.readbyqxmd.com/read/28102732/exacerbating-effects-of-pm2-5-in-ova-sensitized-and-challenged-mice-and-the-expression-of-trpa1-and-trpv1-protein-in-lung
#10
Hong Liu, Xinsheng Fan, Naiqian Wang, Yuyan Zhang, Jinghua Yu
OBJECTIVE: To investigate the effects of PM2.5 on asthma-related phenotypes and on the expression of TRPA1, V1 protein in lung in a mouse model of asthma. METHODS: Female Balb/c mice were utilized to establish 28 and 42 day asthma models. Mice were sensitized with OVA and challenged with OVA, OVA plus normal saline (NS), or OVA plus PM2.5 at two doses, 1.6 mg·kg(-1) or 8.0 mg·kg(-1). PM2.5 was administrated by intratracheal instillationwithout anesthesia. 24 hours after the final OVA challenge changes in airway resistance (RI) and lung compliance (Cdyn) in response to acetylcholine chloride (ACH) were evaluated, and blood, bronchoalveolar lavage fluid (BALF) and lung tissue samples were taken...
January 19, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/28102288/acetylcholine-acts-through-m3-muscarinic-receptor-to-activate-the-egfr-signaling-and-promotes-gastric-cancer-cell-proliferation
#11
Huangfei Yu, Hongwei Xia, Qiulin Tang, Huanji Xu, Guoqing Wei, Ying Chen, Xinyu Dai, Qiyong Gong, Feng Bi
Acetylcholine (ACh), known as a neurotransmitter, regulates the functions of numerous fundamental central and peripheral nervous system. Recently, emerging evidences indicate that ACh also plays an important role in tumorigenesis. However, little is known about the role of ACh in gastric cancer. Here, we reported that ACh could be auto-synthesized and released from MKN45 and BGC823 gastric cancer cells. Exogenous ACh promoted cell proliferation in a does-dependent manner. The M3R antagonist 4-DAMP, but not M1R antagonist trihexyphenidyl and M2/4 R antagonist AFDX-116, could reverse the ACh-induced cell proliferation...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28102047/adequate-tacrolimus-concentration-for-myasthenia-gravis-treatment
#12
T Kanai, A Uzawa, N Kawaguchi, K Himuro, F Oda, Y Ozawa, S Kuwabara
BACKGROUND AND PURPOSE: A single, oral dose of 3 mg/day tacrolimus, approved for myasthenia gravis (MG) treatment in Japan, was shown to reduce steroid dose and anti-acetylcholine receptor (AChR) antibody titers as well as to improve MG symptoms. However, no studies have investigated the association between tacrolimus concentration and its clinical efficacy in MG. In this study, we aimed to determine the optimal tacrolimus concentration for MG treatment. METHODS: The trough tacrolimus concentration in 51 patients with MG (positive for anti-AChR antibody, n = 48; negative for anti-AChR and anti-muscle-specific tyrosine kinase antibodies, n = 3) who received 3 mg/day tacrolimus for more than 1 year was measured using a chemiluminescent enzyme immunoassay...
February 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/28101995/cholinergic-signaling-in-myelination
#13
REVIEW
R Douglas Fields, Dipankar J Dutta, Jillian Belgrad, Maya Robnett
There is a long history of research on acetylcholine (ACh) function in myelinating glia, but a resurgence of interest recently as a result of the therapeutic potential of manipulating ACh signaling to promote remyelination, and the broader interest in neurotransmitter signaling in activity-dependent myelination. Myelinating glia express all the major types of muscarinic and nicotinic ACh receptors at different stages of development, and acetylcholinesterase and butyrylcholinesterase are highly expressed in white matter...
January 19, 2017: Glia
https://www.readbyqxmd.com/read/28101715/cortex-and-amygdala-dependent-learning-and-nicotinic-acetylcholine-receptor-gene-expression-is-severely-impaired-in-mice-orally-treated-with-alcl3
#14
Syeda Mehpara Farhat, Aamra Mahboob, Touqeer Ahmed
Recent industrialization has increased human exposure to bio-available aluminum (Al). If more Al enters the brain than leaves, Al concentration will rise in the brain leading to neurodegenerative disorders. The aim of the present study was to determine Al concentration, neurodegeneration, and nicotinic acetylcholine receptor (nAChR) gene expression in the cortex and amygdala after oral ingestion of Al salt. The effect of Al on cortex- and amygdala-dependent learning and memory functions was also assessed. Mice were given AlCl3 (250 mg/kg) in drinking water for 42 days...
January 18, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28100642/isoform-specific-mechanisms-of-%C3%AE-3%C3%AE-4-nicotinic-acetylcholine-receptor-modulation-by-the-prototoxin-lynx1
#15
Andrew A George, Abigail Bloy, Julie M Miwa, Jon M Lindstrom, Ronald J Lukas, Paul Whiteaker
This study investigates-for the first time to our knowledge-the existence and mechanisms of functional interactions between the endogenous mammalian prototoxin, lynx1, and α3- and β4-subunit-containing human nicotinic acetylcholine receptors (α3β4*-nAChRs). Concatenated gene constructs were used to express precisely defined α3β4*-nAChR isoforms (α3β4)2β4-, (α3β4)2α3-, (α3β4)2α5(398D)-, and (α3β4)2α5(398N)-nAChR in Xenopus oocytes. In the presence or absence of lynx1, α3β4*-nAChR agonist responses were recorded by using 2-electrode voltage clamp and single-channel electrophysiology, whereas radioimmunolabeling measured cell-surface expression...
January 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28099964/advancing-age-decreases-pressure-sensitive-modulation-of-calcium-signaling-in-the-endothelium-of-intact-and-pressurized-arteries
#16
Calum Wilson, Christopher D Saunter, John M Girkin, John G McCarron
Aging is the summation of many subtle changes which result in altered cardiovascular function. Impaired endothelial function underlies several of these changes and precipitates plaque development in larger arteries. The endothelium transduces chemical and mechanical signals into changes in the cytoplasmic calcium concentration to control vascular function. However, studying endothelial calcium signaling in larger arteries in a physiological configuration is challenging because of the requirement to focus through the artery wall...
January 19, 2017: Journal of Vascular Research
https://www.readbyqxmd.com/read/28099246/paradoxical-emergence-administration-of-subanesthetic-ketamine-during-isoflurane-anesthesia-induces-burst-suppression-but-accelerates-recovery
#17
Viviane S Hambrecht-Wiedbusch, Duan Li, George A Mashour
BACKGROUND: Promoting arousal by manipulating certain brain regions and/or neurotransmitters has been a recent research focus, with the goal of trying to improve recovery from general anesthesia. The current study tested the hypothesis that a single subanesthetic dose of ketamine during isoflurane anesthesia would increase cholinergic tone in the prefrontal cortex and accelerate recovery. METHODS: Adult male rats were implanted with electroencephalography electrodes (frontal, parietal, and occipital cortex) and a microdialysis guide cannula targeted for the prefrontal cortex...
January 18, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28098791/development-of-high-throughput-method-for-measurement-of-vascular-nitric-oxide-generation-in-microplate-reader
#18
Soad S Abd El-Hay, Christa L Colyer
BACKGROUND: Despite the importance of nitric oxide (NO) in vascular physiology and pathology, a high-throughput method for the quantification of its vascular generation is lacking. OBJECTIVE: By using the fluorescent probe 4-amino-5-methylamino-2',7'-difluorofluorescein (DAF-FM), we have optimized a simple method for the determination of the generation of endothelial nitric oxide in a microplate format. METHODS: A nitric oxide donor was used (3-morpholinosydnonimine hydrochloride, SIN-1)...
January 13, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28097486/the-therapeutic-effectiveness-of-delayed-fetal-spinal-cord-tissue-transplantation-on-respiratory-function-following-mid-cervical-spinal-cord-injury
#19
Chia-Ching Lin, Sih-Rong Lai, Yu-Han Shao, Chun-Lin Chen, Kun-Ze Lee
Respiratory impairment due to damage of the spinal respiratory motoneurons and interruption of the descending drives from brainstem premotor neurons to spinal respiratory motoneurons is the leading cause of morbidity and mortality following cervical spinal cord injury. The present study was designed to evaluate the therapeutic effectiveness of delayed transplantation of fetal spinal cord (FSC) tissue on respiratory function in rats with mid-cervical spinal cord injury. Embryonic day-14 rat FSC tissue was transplanted into a C4 spinal cord hemilesion cavity in adult male rats at 1 week postinjury...
January 17, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28096851/acetylcholinesterase-inhibitor-improves-learning-and-memory-impairment-induced-by-toxoplasma-gondii-infection
#20
Hossein Mahmoudvand, Vahid Sheibani, Hossein Keshavarz, Saeedeh Shojaee, Khadijeh Esmaeelpour, Naser Ziaali
BACKGROUND: Here, we established the mouse models of chronic toxoplasmosis by T. gondii Tehran strain to provide a good understanding about defining the possible association between T. gondii exposure and learning and memory impairments. Moreover, as secondary objective of the present study, we hypothesized whether administration of an acetylcholinesterase (AChE) inhibitor could reduce learning and memory impairments induced by T. gondii infection. METHODS: Twenty-four male BALB/c mice were used to establishment of latent toxoplasmosis...
April 2016: Iranian Journal of Parasitology
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