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https://www.readbyqxmd.com/read/28431901/clozapine-reduces-toll-like-receptor-4-nf-%C3%AE%C2%BAb-mediated-inflammatory-responses-through-inhibition-of-calcium-calmodulin-dependent-akt-activation-in-microglia
#1
Seunghyun Jeon, Se Hyun Kim, Soon Young Shin, Young Han Lee
Clozapine is an atypical antipsychotic agent used in the treatment of schizophrenia and severe mood disorders. Accumulating evidence suggests that neuroinflammation is closely associated with the pathogenesis of various neurodegenerative diseases and psychiatric disorders. Clozapine exerts anti-inflammatory activity. However, the molecular mechanism underlying the anti-inflammatory activity of clozapine is poorly understood. In this study, we found that clozapine suppressed lipopolysaccharide (LPS)-induced phosphorylation of IκBα at Ser-32 and of p65/RelA at Ser-468, as well as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-dependent transcriptional activity in microglial cells...
April 18, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28423696/improvement-of-dexamethasone-sensitivity-by-chelation-of-intracellular-ca2-in-pediatric-acute-lymphoblastic-leukemia-cells-through-the-prosurvival-kinase-erk1-2-deactivation
#2
Souleymane Abdoul-Azize, Isabelle Dubus, Jean-Pierre Vannier
Previous studies have demonstrated that glucocorticoid hormones, including dexamethasone, induced alterations in intracellular calcium homeostasis in acute lymphoblastic leukemia (ALL) cells. However, the mechanism by which intracellular calcium homeostasis participates in dexamethasone sensitivity and resistance on ALL cells remains elusive. Here, we found that treatment of cells with dexamethasone resulted in increased intracellular calcium concentrations through store-operated calcium entry stimulation, which was curtailed by store-operated calcium channel blockers...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28419922/cadmium-induces-ca-2-mediated-calpain-1-caspase-3-dependent-apoptosis-in-primary-cultured-rat-proximal-tubular-cells
#3
Hong Wang, Nianhui Zhai, Ying Chen, Haibin Xu, Kehe Huang
Calcium, as a ubiquitous second messenger, governs a large array of cellular processes and is necessary for cell survival. More recently, it was observed that the cytosolic Ca(2+) concentration ([Ca(2+)]c) elevation could induce apoptosis in primary cultured rat proximal tubular (rPT) cells exposed to cadmium (Cd), but the concrete mechanism is still unclear. This study was designed to investigate the signal pathway involved in [Ca(2+)]c elevation-mediated apoptosis. The results confirmed the elevation of [Ca(2+)]c by confocal microscopy and enhancement of the apoptosis by Hoechst 33258 staining and flow cytometer when rPT cells were exposed to Cd for 12h...
April 8, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28417537/the-effects-and-mechanism-of-action-of-methane-on-ileal-motor-function
#4
Y M Park, Y J Lee, Z Hussain, Y H Lee, H Park
BACKGROUND: Methane has been associated with constipation-predominant irritable bowel syndrome, slowing intestinal transit time by augmenting contractile activity. However, the precise mechanism underlying this effect remains unclear. Therefore, we investigated the mechanisms underlying the effect of methane on contractile activity, and whether such effects are mediated by nerve impulses or muscular contraction. METHODS: We connected guinea pig ileal muscle strips to a force/tension transducer and measured amplitudes of contraction in response to electrical field stimulation (EFS; 1, 2, 8, 16 Hz) following methane infusion in the presence of tetradotoxin (TTX), atropine, guanethidine, or GR 113808...
April 18, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28414098/cytosolic-calcium-mediates-rip1-rip3-complex-dependent-necroptosis-through-jnk-activation-and-mitochondrial-ros-production-in-human-colon-cancer-cells
#5
Wen Sun, Xiaxia Wu, Hongwei Gao, Jie Yu, Wenwen Zhao, Jin-Jian Lu, Jinhua Wang, Guanhua Du, Xiuping Chen
Necroptosis is a form of programmed necrosis mediated by signaling complexes with receptor-interacting protein 1 (RIP1) and RIP3 kinases as the main mediators. However, the underlying execution pathways of this phenomenon have yet to be elucidated in detail. In this study, a RIP1/RIP3 complex was formed in 2-methoxy-6-acetyl-7-methyljuglone (MAM)-treated HCT116 and HT29 colon cancer cells. With this formation, mitochondrial reactive oxygen species (ROS) levels increased, mitochondrial depolarization occurred, and ATP concentrations decreased...
April 14, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28410965/permissive-role-of-reduced-inwardly-rectifying-potassium-current-density-in-the-automaticity-of-the-guinea-pig-pulmonary-vein-myocardium
#6
Yayoi Tsuneoka, Masahiko Irie, Yusuke Tanaka, Takahiko Sugimoto, Yuka Kobayashi, Taichi Kusakabe, Keisuke Kato, Shogo Hamaguchi, Iyuki Namekata, Hikaru Tanaka
The electrophysiological properties underlying the automaticity of the guinea pig pulmonary vein myocardium were studied. About 30% of the isolated pulmonary vein tissue preparations showed spontaneous electrical activity, as shown by glass microelectrode recordings from their myocardial layer. The remaining quiescent preparations had a resting membrane potential less negative than that in the left atria. Blockade of the acetylcholine activated potassium current (IK-ACh) by tertiapin induced a depolarizing shift of the resting membrane potential and automatic electrical activity in the pulmonary vein, but not in the atria...
March 28, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28393957/photo-cleavable-analog-of-bapta-for-the-fast-and-efficient-release-of-ca-2
#7
Mariia V Sutton, Matthew McKinley, Revathy Kulasekharan, Vladimir V Popik
A new photocleavable analog of BAPTA chelating ligand has a high affinity towards Ca(2+) ions (K = 2.5 × 10(6) M(-1)). The use of photolabile 3-(hydroxymethyl)-2-naphthol core in the design of photo-BAPTA allows for the efficient (Φ = 0. 63) and very fast (τ < 12 μs) release of Ca(2+) ions upon 300 or 350 nm irradiation.
April 10, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28384516/effects-of-puerarin-on-intracellular-ca-2-and-cell-viability-of-mdck-renal-tubular-cells
#8
He-Hsiung Cheng, Chiang-Ting Chou, Wei-Zhe Liang, Chun-Chi Kuo, Pochuan Shieh, Jue-Long Wang, Chung-Ren Jan
Puerarin is a natural compound and has been used as herb medication in a number of countries, especially in Asia. The effect of puerarin on Ca(2+) signaling is unknown in renal cells. This study examined whether puerarin affected Ca(2+) physiology in MDCK renal tubular cells. Cytosolic free Ca(2+) levels ([Ca(2+)]i) were measured using the fluorescent dye fura-2. Cell viability was examined by using WST-1 assay. Puerarin induced [Ca(2+)]i rises and the response was reduced by removing extracellular Ca(2+). Puerarin-induced Ca(2+) entry was not altered by protein kinase C (PKC) activity, but was inhibited by nifedipine...
March 24, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28374913/liposomes-as-a-putative-tool-to-investigate-naadp-signaling-in-vasculogenesis
#9
Francesca Di Nezza, Estella Zuccolo, Valentina Poletto, Vittorio Rosti, Antonio De Luca, Francesco Moccia, Germano Guerra, Luigi Ambrosone
Nicotinic acid adenine dinucleotide phosphate (NAADP) is the newest discovered intracellular second messengers, which is able to release Ca(2+) stored within endolysosomal (EL) vesicles. NAADP-induced Ca(2+) signals mediate a growing number of cellular functions, ranging from proliferation to muscle contraction and differentiation. Recently, NAADP has recently been shown to regulate angiogenesis by promoting endothelial cell growth. It is, however, still unknown whether NAADP stimulates proliferation also in endothelial progenitor cells, which are mobilized in circulation after an ischemic insult to induce tissue revascularization...
April 4, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28374834/glycation-of-paraoxonase-1-by-high-glucose-instigates-endoplasmic-reticulum-stress-to-induce-endothelial-dysfunction-in-vivo
#10
Wei Yu, Xiaoli Liu, Liru Feng, Hui Yang, Weiye Yu, Tiejian Feng, Shuangxi Wang, Jun Wang, Ning Liu
High-density lipoprotein (HDL) modulates low-density lipoprotein and cell membrane oxidation through the action of paraoxonase-1 (PON1). Endoplasmic reticulum (ER) stress has been linked to a wide range of human pathologies including diabetes, obesity, and atherosclerosis. Previous studies have reported that PON1 is glycated in diabetes. The aim of this study is to investigate whether and how PON1 glycation contributes to endothelial dysfunction in diabetes. ER stress markers were monitored by western blot...
April 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28371805/restitution-slope-is-principally-determined-by-steady-state-action-potential-duration
#11
Michael J Shattock, Kyung Chan Park, Hsiang-Yu Yang, Angela Wc Lee, Steve Niederer, Kenneth T MacLeod, James Winter
AimsThe steepness of the action potential duration (APD) restitution curve and local tissue refractoriness are both thought to play important roles in arrhythmogenesis. Despite this, there has been little recognition of the apparent association between steady-state APD and the slope of the restitution curve. The objective of this study was to test the hypothesis that restitution slope is determined by APD and to examine the relationship between restitution slope, refractoriness and susceptibility to VF.Methods and ResultsExperiments were conducted in isolated hearts and ventricular myocytes from adult guinea pigs and rabbits...
March 23, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28369952/a-calcium-dependent-pathway-underlies-activity-dependent-plasticity-of-electrical-synapses-in-the-thalamic-reticular-nucleus
#12
Jessica Sevetson, Sarah Fittro, Emily Heckman, Julie S Haas
Recent results have demonstrated modification of electrical synapse strength by varied forms of neuronal activity. However, the mechanisms underlying plasticity induction in central mammalian neurons are unclear. Here we show that the two established inductors of plasticity at electrical synapses in the thalamic reticular nucleus - paired burst spiking in coupled neurons, and mGluR-dependent tetanization of synaptic input - are separate pathways that converge at a common downstream endpoint. Using occlusion experiments and pharmacology in patched pairs of coupled neurons in vitro, we show that burst-induced depression depends on calcium entry via voltage-gated channels, is blocked by BAPTA chelation, and recruits intracellular calcium release on its way to activation of phosphatase activity...
March 29, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28347754/cadmium-disrupts-autophagic-flux-by-inhibiting-cytosolic-ca-2-dependent-autophagosome-lysosome-fusion-in-primary-rat-proximal-tubular-cells
#13
Fei Liu, Xin-Yu Wang, Xu-Ping Zhou, Zong-Ping Liu, Xiang-Bin Song, Zhen-Yong Wang, Lin Wang
Previous studies have shown that subcellular Ca(2+) redistribution is involved in Cd-induced autophagy inhibition in primary rat proximal tubular (rPT) cells, but the mechanism remains unclear. In this study, the status of autophagic flux was monitored by the GFP and RFP tandemly tagged LC3 method. Pharmacological inhibition of cytosolic Ca(2+) concentration ([Ca(2+)]c) with 2-APB or BAPTA-AM significantly alleviated Cd-elevated yellow puncta formation and restored Cd-inhibited red puncta formation, while thapsigargin (TG) had the opposite regulatory effect, demonstrating that Cd-induced [Ca(2+)]c elevation inhibited the autophagic flux in rPT cells...
March 25, 2017: Toxicology
https://www.readbyqxmd.com/read/28337305/rho-kinase-regulates-neurite-outgrowth-of-hippocampal-neurons-via-calcium-dependent-cytoskeleton-regulation
#14
Zhisheng Ji, Zhenbin Cai, Jifeng Zhang, Nannuan Liu, Jing Chen, Minghui Tan, Hongsheng Lin, Guoqing Guo
OBJECTIVE: To investigate whether calcium is involved in downstream signal transduction in neurite outgrowth regulated by Rho kinase. METHODS: In vitro primary hippocampal neurons were cultured and treated with Rho kinase agonist (LPA) or antagonist (Y-27632). Then, the cytoskeleton and neurite outgrowth were observed. After addition of calcium antagonist BAPTA/AM to reduce intracellular calcium, the cytoskeleton distribution and neurite outgrowth were observed...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28334325/endocannabinoid-dependent-long-term-potentiation-of-synaptic-transmission-at-rat-barrel-cortex
#15
Laura Eva Maglio, José Antonio Noriega-Prieto, Maria Jesús Maraver, David Fernández de Sevilla
Brain-derived neurotrophic factor (BDNF) plays a critical role in modulating plasticity in sensory cortices. Indeed, a BDNF-dependent long-term potentiation (LTP) at distal basal excitatory synapses of Layer 5 pyramidal neurons (L5PNs) has been demonstrated in disinhibited rat barrel cortex slices. Although it is well established that this LTP requires the pairing of excitatory postsynaptic potentials (PSPs) with Ca2+ spikes, its induction when synaptic inhibition is working remains unexplored. Here we show that low-frequency stimulation at basal dendrites of L5PNs is able to trigger a PSP followed by an action potential (AP) and a slow depolarization (termed PSP-Ca2+ response) in thalamocortical slices without blocking synaptic inhibition...
March 1, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28332205/evidence-that-5-ht-stimulates-intracellular-ca-2-signalling-and-activates-pannexin-1-currents-in-type-ii-cells-of-the-rat-carotid-body
#16
Sindhubarathi Murali, Min Zhang, Colin A Nurse
Carotid body (CB) chemoreceptor (type I) cells can synthesize and release 5-hydroxytryptamine (5-HT) and increased autocrine-paracrine 5-HT2 receptor signalling contributes to sensory long-term facilitation during chronic intermittent hypoxia (CIH). However, recent studies suggest that adjacent glial-like type II cells can respond to CB paracrine signals by elevating intracellular calcium (Δ[Ca(2+) ]i ) and activating carbenoxolone-sensitive, ATP-permeable, pannexin-1 (Panx-1)-like channels. Here, using dissociated rat CB cultures, we found that 5-HT induced Δ[Ca(2+) ]i responses in a subpopulation of type I cells, and in most (∼67%) type II cells identified by their sensitivity to the P2Y2 receptor agonist, UTP...
March 22, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28299994/the-changes-of-cytoskeletal-proteins-induced-by-the-fast-effect-of-estrogen-in-mouse-blastocysts-and-its-roles-in-implantation
#17
Shi-Mao Zhang, Lin-Lin Yu, Ting Qu, Ying Hu, Dong-Zhi Yuan, Sheng Zhang, Qian Xu, You-Bo Zhao, Jin-Hu Zhang, Li-Min Yue
It is necessary for estrogen to activate mouse blastocysts, so that they can attach to endometrial epithelium in implantation and in our previous research, we have proved estrogen can induce a fast increase in intracellular calcium of mouse blastocysts through acting on G protein-coupled receptor 30 (GPR30), which further promotes their implantation. Moreover, there has been evidence that cytoskeletal proteins are involved in integrin-mediated adhesion of many kinds of cells, which also plays an important role in implantation...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28296171/calcium-dependent-nedd4-2-upregulation-mediates-degradation-of-the-cardiac-sodium-channel-nav1-5-implications-for-heart-failure
#18
Ling Luo, Feifei Ning, Yuan Du, Bingxue Song, Dandan Yang, Samantha C Salvage, Ya Wang, James A Fraser, Shetuan Zhang, Aiqun Ma, Tingzhong Wang
AIM: Reductions of voltage-gated sodium channel (Nav1.5) function/expression provide a slowed-conduction substrate for cardiac arrhythmias. Nedd4-2, which is activated by calcium, post-translationally modulates Nav1.5. We aim to investigate whether elevated intracellular calcium ([Ca(2+) ]i ) reduces Nav1.5 through Nedd4-2 and its role in heart failure (HF). METHODS: Using a combination of biochemical, electrophysiological, cellular and in vivo methods, we tested the effect and mechanism of calcium on Nedd4-2 and in turn Nav1...
March 10, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28293167/melatonin-mediates-protective-effects-against-kainic-acid-induced-neuronal-death-through-safeguarding-er-stress-and-mitochondrial-disturbance
#19
Feixiao Xue, Cai Shi, Qingjie Chen, Weijian Hang, Liangtao Xia, Yue Wu, Sophia Z Tao, Jie Zhou, Anbing Shi, Juan Chen
Kainic acid (KA)-induced neuronal death is linked to mitochondrial dysfunction and ER stress. Melatonin is known to protect hippocampal neurons from KA-induced apoptosis, but the exact mechanisms underlying melatonin protective effects against neuronal mitochondria disorder and ER stress remain uncertain. In this study, we investigated the sheltering roles of melatonin during KA-induced apoptosis by focusing on mitochondrial dysfunction and ER stress mediated signal pathways. KA causes mitochondrial dynamic disorder and dysfunction through calpain activation, leading to neuronal apoptosis...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28274857/bapta-am-decreases-cellular-ph-inhibits-acidocalcisome-acidification-and-autophagy-in-amino-acid-starved-t-brucei
#20
Feng-Jun Li, Kevin S W Tan, Cynthia Y He
To investigate the role of Ca(2+) signaling in starvation-induced autophagy in Trypanosoma brucei, the causative agent of human African trypanosomiasis, we used cell-permeant Ca(2+) chelator BAPTA-AM and cell impermeant chelator EGTA, and examined the potential involvement of several intracellular Ca(2+) signaling pathways in T. brucei autophagy. The results showed an unexpected effect of BAPTA-AM in decreasing cellular pH and inhibiting acidocalcisome acidification in starved cells. The implication of these results in the role of Ca(2+) signaling and cellular/organellar pH in T...
April 2017: Molecular and Biochemical Parasitology
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