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https://www.readbyqxmd.com/read/28687341/carbenoxolone-prevents-chemical-eye-ischemia-reperfusion-induced-cell-death-via-11%C3%AE-hydroxysteroid-dehydrogenase-type-1-inhibition
#1
Kyoung-Jin Choi, Yoon-Ju Na, Sung Bum Park, Won Hoon Jung, Hye-Rim Sung, Ki Young Kim
Glaucoma is one of the leading causes of preventable blindness diseases, affecting more than 2 million people in the United States. Recently, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors were found to exert preventive effects against glaucoma. Therefore, we investigated whether carbenoxolone (CBX), an 11β-HSD1 inhibitor, prevents chemical ischemia-reperfusion-induced cell death in human trabecular meshwork (HTM) cells. The present study demonstrated that CBX inhibited cell death caused by iodoacetic acid (IAA)-induced ischemia-reperfusion, and its effect was associated with the inhibition of 11β-HSD1 expression and activity...
July 4, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28685011/methylglyoxal-induces-changes-in-the-glyoxalase-system-and-impairs-glutamate-uptake-activity-in-primary-astrocytes
#2
Fernanda Hansen, Fabiana Galland, Franciane Lirio, Daniela Fraga de Souza, Carollina Da Ré, Rafaela Ferreira Pacheco, Adriana Fernanda Vizuete, André Quincozes-Santos, Marina Concli Leite, Carlos-Alberto Gonçalves
The impairment of astrocyte functions is associated with diabetes mellitus and other neurodegenerative diseases. Astrocytes have been proposed to be essential cells for neuroprotection against elevated levels of methylglyoxal (MG), a highly reactive aldehyde derived from the glycolytic pathway. MG exposure impairs primary astrocyte viability, as evaluated by different assays, and these cells respond to MG elevation by increasing glyoxalase 1 activity and glutathione levels, which improve cell viability and survival...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28652220/inhibition-of-alzheimer-s-amyloid-beta-aggregation-in-vitro-by-carbenoxolone-insight-into-mechanism-of-action
#3
Sheetal Sharma, Bimla Nehru, Avneet Saini
BACKGROUND: The major hallmark of Alzheimer's disease (AD) is the formation of amyloid aggregates, which are formed due to improper folding of proteins leading to the aggregation of amyloid beta (Aβ) 42 peptide. Inhibition of Aβ 42 aggregation using a drug such as carbenoxolone (Cbx), which has already been stated as neuroprotective, appears to be an effective approach against AD. OBJECTIVE: The present study was designed to investigate the anti-fibrillation activity of Cbx against the Aβ 42 aggregation...
June 24, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28631948/possible-contribution-of-pannexin-1-to-capsaicin-induced-atp-release-in-rat-nasal-columnar-epithelial-cells
#4
Toyoaki Ohbuchi, Ba Hung Do, Hiroki Koizumi, Shoko Takeuchi, Yoichi Ueta, Hideaki Suzuki
Current evidence indicates that transient receptor potential (TRP) channel activity involves a relationship between opening of pannexin-1 and release of ATP into the extracellular space. We examined the effects of agonists of thermosensitive TRP channels (TRPM8, TRPA1, TRPV1, and TRPV2) on ATP release from rat nasal mucosa, and measured ciliary beat frequency (CBF) using digital high-speed video imaging. Single-cell patch clamping from dissociated rat nasal columnar epithelial cells was performed to confirm the relationship between pannexin-1 and TRP...
February 10, 2017: Channels
https://www.readbyqxmd.com/read/28628134/-effects-of-silver-nanoparticle-on-hemichannel-activation-and-anti-proliferation-in-hacat-cells
#5
D Yang, J H Xu, F R Deng, X B Guo
OBJECTIVE: To investigate the effect of silver nanoparticles (AgNPs) on hemichannel activity in human skin keratinocytes (HaCaT) and to explore the role of hemichannel in AgNP-induced anti-proliferative effect on HaCaT cells. METHODS: HaCaT cells were exposed to 0, 0.1, 0.2, 1.0, 5.0, 10.0, 15.0 and 20.0 μg/cm(2) of AgNPs for 24 h and cell viability was assessed by propidium iodide (PI) staining with flow cytometry. Hemichannel activity was examined by ethidium bromide (EB) uptake experiments in cells exposed to AgNPs with and without hemichannel inhibitor carbenoxolone (CBX)...
June 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/28617431/nicotine-protects-rat-hypoglossal-motoneurons-from-excitotoxic-death-via-downregulation-of-connexin-36
#6
Silvia Corsini, Maria Tortora, Rossana Rauti, Andrea Nistri
Motoneuron disease including amyotrophic lateral sclerosis may be due, at an early stage, to deficit in the extracellular clearance of the excitatory transmitter glutamate. A model of glutamate-mediated excitotoxic cell death based on pharmacological inhibition of its uptake was used to investigate how activation of neuronal nicotinic receptors by nicotine may protect motoneurons. Hypoglossal motoneurons (HMs) in neonatal rat brainstem slices were exposed to the glutamate uptake blocker DL-threo-β-benzyloxyaspartate (TBOA) that evoked large Ca(2+) transients time locked among nearby HMs, whose number fell by about 30% 4 h later...
June 15, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28589517/inhibition-of-gap-junction-elevates-glutamate-uptake-in-cultured-astrocytes
#7
Katsura Takano, Masato Ogawa, Kenji Kawabe, Mitsuaki Moriyama, Yoichi Nakamura
Glutamate uptake is a main function of astrocytes to keep extracellular glutamate levels low and protect neurons against glutamate-induced excitotoxicity. On the other hand, astrocyte networks formed by gap junctions, which are consisted with connexins and connecting neighboring cells, are reported to play a critical role in maintaining the homeostasis in the brain. In the present study, we examined the effects of gap junction inhibitors on the glutamate uptake activity in cultured rat cortical astrocytes. At first, we confirmed the effects of gap junction inhibitors, 1-octanol and carbenoxolone, on cell-cell communication by the scrape-loading assay using a fluorescent dye Lucifer yellow...
June 7, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28585113/sex-dependent-glial-signaling-in-pathological-pain-distinct-roles-of-spinal-microglia-and-astrocytes
#8
Gang Chen, Xin Luo, M Yawar Qadri, Temugin Berta, Ru-Rong Ji
Increasing evidence suggests that spinal microglia regulate pathological pain in males. In this study, we investigated the effects of several microglial and astroglial modulators on inflammatory and neuropathic pain following intrathecal injection in male and female mice. These modulators were the microglial inhibitors minocycline and ZVEID (a caspase-6 inhibitor) and the astroglial inhibitors L-α-aminoadipate (L-AA, an astroglial toxin) and carbenoxolone (a connexin 43 inhibitor), as well as U0126 (an ERK kinase inhibitor) and D-JNKI-1 (a c-Jun N-terminal kinase inhibitor)...
June 5, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28488330/inhibition-of-cx43-mediates-protective-effects-on-hypoxic-reoxygenated-human-neuroblastoma-cells
#9
Nunzio Vicario, Giovanna Calabrese, Agata Zappalà, Carmela Parenti, Stefano Forte, Adriana Carol Eleonora Graziano, Luca Vanella, Rosalia Pellitteri, Venera Cardile, Rosalba Parenti
Olfactory ensheathing cells (OECs), a special population of glial cells, are able to synthesise several trophic factors exerting a neuroprotective action and promoting growth and functional recovery in both in vitro and in vivo models. In the present work, we investigated the neuroprotective effects of OEC-conditioned medium (OEC-CM) on two different human neuron-like cell lines, SH-SY5Y and SK-N-SH (neuroblastoma cell lines), under normoxic and hypoxic conditions. In addition, we also focused our attention on the role of connexins (Cxs) in the neuroprotective processes...
May 9, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28429070/properties-of-synchronous-spontaneous-ca-2-transients-in-the-mural-cells-of-rat-rectal-arterioles
#10
Retsu Mitsui, Hikaru Hashitani
Synchrony of spontaneous Ca(2+) transients among venular mural cells (smooth muscle cells and pericytes) in visceral organs relies on the intercellular spread of L-type voltage-dependent Ca(2+) channel (LVDCC)-dependent depolarisations. However, the mechanisms underlying the synchrony of spontaneous Ca(2+) transients between arteriolar mural cells are less understood. The spontaneous intracellular Ca(2+) dynamics of arteriolar mural cells in the rat rectal submucosa were visualised by Cal-520 Ca(2+) imaging to analyse their synchrony...
April 21, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28422293/an-autocrine-atp-release-mechanism-regulates-basal-ciliary-activity-in-airway-epithelium
#11
Karla Droguett, Mariana Rios, Daniela V Carreño, Camilo Navarrete, Christian Fuentes, Manuel Villalón, Nelson P Barrera
KEY POINTS: Extracellular ATP, in association with [Ca(2+) ]i regulation, is required to maintain basal ciliary beat frequency. Increasing extracellular ATP levels increases ciliary beating in airway epithelial cells, maintaining a sustained response by inducing the release of additional ATP. Extracellular ATP levels in the millimolar range, previously associated with pathophysiological conditions of the airway epithelium, produce a transient arrest of ciliary activity. The regulation of ciliary beat frequency is dependent on ATP release by hemichannels (connexin/pannexin) and P2X receptor activation, the blockage of which may even stop ciliary movement...
July 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28421552/gap-junction-modulation-of-low-frequency-oscillations-in-the-cerebellar-granule-cell-layer
#12
Jennifer Claire Robinson, C Andrew Chapman, Richard Courtemanche
Local field potential (LFP) oscillations in the granule cell layer (GCL) of the cerebellar cortex have been identified previously in the awake rat and monkey during immobility. These low-frequency oscillations are thought to be generated through local circuit interactions between Golgi cells and granule cells within the GCL. Golgi cells display rhythmic firing and pacemaking properties, and also are electrically coupled through gap junctions within the GCL. Here, we tested if gap junctions in the rat cerebellar cortex contribute to the generation of LFP oscillations in the GCL...
April 18, 2017: Cerebellum
https://www.readbyqxmd.com/read/28415753/high-mobility-group-box-1-antagonist-limits-metastatic-seeding-in-the-lungs-via-reduction-of-cell-cell-adhesion
#13
Adi Karsch-Bluman, Benzion Amoyav, Nethanel Friedman, Hila Shoval, Ouri Schwob, Ezra Ella, Ori Wald, Ofra Benny
Metastatic spread is the leading cause for cancer-related mortality, with the lungs being a major site for metastatic seeding. Available therapies for patients with metastatic disease are extremely limited. Therefore, there is a desperate need for new strategies to prevent or limit metastatic dissemination and treat existing metastases. The metastatic cascade is highly complex and is affected by multiple factors related to both tumor cells themselves and the microenvironment in the future site of metastasis...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28401401/modulation-of-tonic-gaba-currents-by-anion-channel-and-connexin-hemichannel-antagonists
#14
Christopher B Ransom, Zucheng Ye, William J Spain, George B Richerson
Anion channels and connexin hemichannels are permeable to amino acid neurotransmitters. It is hypothesized that these conductive pathways release GABA, thereby influencing ambient GABA levels and tonic GABAergic inhibition. To investigate this, we measured the effects of anion channel/hemichannel antagonists on tonic GABA currents of rat hippocampal neurons. In contrast to predictions, blockade of anion channels and hemichannels with NPPB potentiated tonic GABA currents of neurons in culture and acute hippocampal slices...
April 12, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28400257/phase-amplitude-coupled-persistent-theta-and-gamma-oscillations-in-rat-primary-motor-cortex-in%C3%A2-vitro
#15
Nicholas W Johnson, Mazhar Özkan, Adrian P Burgess, Emma J Prokic, Keith A Wafford, Michael J O'Neill, Stuart D Greenhill, Ian M Stanford, Gavin L Woodhall
In vivo, theta (4-7 Hz) and gamma (30-80 Hz) neuronal network oscillations are known to coexist and display phase-amplitude coupling (PAC). However, in vitro, these oscillations have for many years been studied in isolation. Using an improved brain slice preparation technique we have, using co-application of carbachol (10 μM) and kainic acid (150 nM), elicited simultaneous theta (6.6 ± 0.1 Hz) and gamma (36.6 ± 0.4 Hz) oscillations in rodent primary motor cortex (M1). Each oscillation showed greatest power in layer V...
June 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28390472/pannexin-channels-increase-propidium-iodide-permeability-in-frozen-thawed-dog-spermatozoa
#16
J L Torres, J Palomino, R D Moreno, M De Los Reyes
Pannexins (Panx) are proteins that form functional single membrane channels, but they have not yet been described in dogs. The aim of the present study was to detect Panx1, Panx2 and Panx3 in frozen-thawed dog spermatozoa using flow cytometry and immunofluorescence analyses, evaluating the relationship of these proteins with propidium iodide (PI) in frozen-thawed spermatozoa. Fresh and frozen-thawed dog spermatozoa from eight dogs were preincubated with 3μM PI with or without 15μM carbenoxolone (CBX) or 1mM probenecid (PBD), two Panx channel inhibitors, and then incubated with rabbit anti-Panx1, anti-Panx2 and anti-Panx3 antibodies (1:200)...
April 10, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28369176/glial-calcium-waves-are-triggered-by-seizure-activity-and-not-essential-for-initiating-ictal-onset-or-neurovascular-coupling
#17
Eliza Baird-Daniel, Andy G S Daniel, Michael Wenzel, Dan Li, Jyun-You Liou, Philippe Laffont, Mingrui Zhao, Rafael Yuste, Hongtao Ma, Theodore H Schwartz
It has been postulated that glia play a critical role in modifying neuronal activity, mediating neurovascular coupling, and in seizure initiation. We investigated the role of glia in ictogenesis and neurovascular coupling through wide-field multicell and 2-photon single cell imaging of calcium and intrinsic signal imaging of cerebral blood volume in an in vivo rat model of focal neocortical seizures. Ictal events triggered a slowly propagating glial calcium wave that was markedly delayed after both neuronal and hemodynamic onset...
June 1, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28356735/inhibition-of-gap-junction-intercellular-communication-is-involved-in-silica-nanoparticles-induced-h9c2-cardiomyocytes-apoptosis-via-the-mitochondrial-pathway
#18
Zhong-Jun Du, Guan-Qun Cui, Juan Zhang, Xiao-Mei Liu, Zhi-Hu Zhang, Qiang Jia, Jack C Ng, Cheng Peng, Cun-Xiang Bo, Hua Shao
Gap junction intercellular communication (GJIC) between cardiomyocytes is essential for synchronous heart contraction and relies on connexin-containing channels. Connexin 43 (Cx43) is a major component involved in GJIC in heart tissue, and its abnormal expression is closely associated with various cardiac diseases. Silica nanoparticles (SNPs) are known to induce cardiovascular toxicity. However, the mechanisms through which GJIC plays a role in cardiomyocytes apoptosis induced by SNPs remain unknown. The aim of the present study is to determine whether SNPs-decreased GJIC promotes apoptosis in rat cardiomyocytes cell line (H9c2 cells) via the mitochondrial pathway using CCK-8 Kit, scrape-loading dye transfer technique, Annexin V/PI double-staining assays, and Western blot analysis...
2017: International Journal of Nanomedicine
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
#19
Sindhubarathi Murali, Min Zhang, Colin A Nurse
KEY POINTS: 5-HT is a neuromodulator released from carotid body (CB) chemoreceptor (type I) cells and facilitates the sensory discharge following chronic intermittent hypoxia (CIH). In the present study, we show that, in addition to type I cells, adjacent glial-like type II cells express functional, ketanserin-sensitive 5-HT2 receptors, and their stimulation increases cytoplasmic Ca(2+) derived from intracellular stores. In type II cells, 5-HT activated a ketanserin-sensitive inward current (I5-HT ) that was similar to that (IUTP ) activated by the P2Y2R agonist, UTP...
July 1, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28320863/rac1-gtpase-regulates-11%C3%AE-hydroxysteroid-dehydrogenase-type-2-and-fibrotic-remodeling
#20
Daniel Lavall, Pia Schuster, Nadine Jacobs, Andrey Kazakov, Michael Böhm, Ulrich Laufs
The aim of the study was to characterize the role of Rac1 GTPase for the mineralocorticoid receptor (MR)-mediated pro-fibrotic remodeling. Transgenic mice with cardiac overexpression of constitutively active Rac1 (RacET) develop an age-dependent phenotype with atrial dilatation, fibrosis, and atrial fibrillation. Expression of MR was similar in RacET and WT mice. The expression of 11β hydroxysteroid dehydrogenase type 2 (11β-HSD2) was age-dependently up-regulated in the atria and the left ventricles of RacET mice on mRNA and protein levels...
May 5, 2017: Journal of Biological Chemistry
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