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https://www.readbyqxmd.com/read/28631939/a-high-throughput-screening-assay-for-nkcc1-cotransporter-using-nonradioactive-rubidium-flux-technology
#1
Sikander Gill, Rajwant Gill, Yang Wen, Thilo Enderle, Doris Roth, Dong Liang
A high-throughput screening (HTS) assay was developed for cotransporter, NKCC1, which is a potential target for the treatment of diverse disorders. This nonradioactive rubidium flux assay coupled with ion channel reader series provides a working screen for this target expressed in human embryonic kidney (HEK) cell line. An eightfold window of detection was achieved with the optimized assay. This new functional assay offered a robust working model for NKCC1 in determining reliable and concordant rank orders of the test compounds supporting its sensitivity and specificity...
May 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28577991/inhibition-of-na-k-2cl-cotransporter-attenuates-blood-brain-barrier-disruption-in-a-mouse-model-of-traumatic-brain-injury
#2
Jun Zhang, Hongjian Pu, Haiyue Zhang, Zhishuo Wei, Xiaoyan Jiang, Mingyue Xu, Lili Zhang, Wenting Zhang, Jialin Liu, Hengxing Meng, R Anne Stetler, Dandan Sun, Jun Chen, Yanqin Gao, Ling Chen
Traumatic brain injury (TBI) can lead to long-term motor and cognitive dysfunction, which can be at least partly attributed to blood-brain barrier (BBB) disruption. The mechanisms underlying post-TBI BBB disruption, however, are poorly understood thus far. Na(+)-K(+)-2Cl(-) cotransporter isoform 1 (NKCC1) is a universally expressed ion transporter that maintains intracellular ion homeostasis by increasing intracellular K(+) and Cl(-). Having been characterized in stroke models, NKCC1 is activated in various cell types in the ischemic brain, and is thought to mediate BBB disruption, brain edema, and neuronal cell death...
May 31, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28574574/actions-of-quercetin-a-flavonoid-on-ion-transporters-its-physiological-roles
#3
REVIEW
Yoshinori Marunaka
Flavonoids keep us healthy by controlling various body and cellular functions. It is well known that cations, such as Na(+) , K(+) , and Ca(2+) , play important roles in the regulation of body and cellular functions, including generation of action potentials and the resting membrane potential of neural and muscle cells and signal transduction as intracellular second messengers. However, we have little information on the physiological roles of anions, particularly Cl(-) , in body and cellular functions. Quercetin, a flavonoid, stimulates Na(+) -K(+) -2Cl(-) cotransporter 1 (NKCC1), which is one of the most important ion transporters regulating the cytosolic Cl(-) concentration ([Cl(-) ]c )...
June 2, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28555110/reduced-membrane-insertion-of-clc-k-by-v33l-barttin-results-in-loss-of-hearing-but-leaves-kidney-function-intact
#4
Hua Tan, Stefanie Bungert-Plümke, Christoph Fahlke, Gabriel Stölting
In the mammalian ear, transduction of sound stimuli is initiated by K(+) entry through mechano-sensitive channels into inner hair cells. K(+) entry is driven by a positive endocochlear potential that is maintained by the marginal cell layer of the stria vascularis. This process requires basolateral K(+) import by NKCC1 Na(+)-2Cl(-)-K(+) co-transporters as well as Cl(-) efflux through ClC-Ka/barttin or ClC-Kb/barttin channels. Multiple mutations in the gene encoding the obligatory CLC-K subunit barttin, BSND, have been identified in patients with Bartter syndrome type IV...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28526685/differences-in-molecular-mechanisms-of-k-clearance-in-the-auditory-sensory-epithelium-of-birds-and-mammals
#5
Viviane Wilms, Chris Söffgen, Hans Gerd Nothwang
Mechanoelectrical transduction in the vertebrate inner ear is a highly conserved mechanism depending on K(+) influx into hair cells. Here, we investigated the molecular underpinnings of subsequent K(+) recycling in the chicken basilar papilla and compared it with those in the mammalian auditory sensory epithelium. Like mammals, the avian auditory hair cell uses KCNQ4, KCNMA1, and KCNMB1 as K(+) efflux systems. Expression of KCNQ1 and KCNE1 suggests an additional efflux apparatus in avian hair cells. Marked differences were observed for K(+) clearance...
May 19, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28490320/astaxanthin-protects-astrocytes-against-trauma-induced-apoptosis-through-inhibition-of-nkcc1-expression-via-the-nf-%C3%AE%C2%BAb-signaling-pathway
#6
Mingkun Zhang, Zhenwen Cui, Hua Cui, Yong Wang, Chunlong Zhong
BACKGROUND: Astaxanthin (ATX) is a carotenoid pigment with pleiotropic pharmacological properties that is seen as a possible drug for treating cerebral ischemic injury and subarachnoid hemorrhage. Na(+)-K(+)-2Cl(-) co-transporter-1 (NKCC1), an intrinsic membrane protein expressed by many cell types, is activated by various insults, leading to the formation of cell swelling and brain edema. We previously established that ATX attenuated brain edema and improved neurological outcomes by modulating NKCC1 expression after traumatic brain injury in mice...
May 10, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28488084/loop-diuretics-diminish-hemolysis-induced-by-%C3%AE-hemolysin-from-escherichia-coli
#7
Carl Martin Söderström, Steen K Fagerberg, Mette B Brogaard, Jens Leipziger, Marianne Skals, Helle A Praetorius
Uropathogenic Escherichia coli often produce the virulence factor α-hemolysin (HlyA), and the more severe the infection, the likelier it is to isolate HlyA-producing E. coli from patients. HlyA forms pores upon receptor-independent insertion of the toxin into biological membranes and it has been substantiated that HlyA-induced hemolysis is amplified by toxin-induced ATP release and activation of P2X receptors. Thus, hemolysis inflicted by HlyA is a protracted process involving signal transduction. It consists of early, marked cell shrinkage followed by swelling and eventually lysis...
May 9, 2017: Journal of Membrane Biology
https://www.readbyqxmd.com/read/28473802/the-subiculum-a-potential-site-of-ictogenesis-in-a-neonatal-seizure-model
#8
Xin-Xin Wang, Yong-Hua Li, Hai-Qing Gong, Pei-Ji Liang, Pu-Ming Zhang, Qin-Chi Lu
Studies have reported that the subiculum is one origin of interictal-like discharges in adult patients with temporal lobe epilepsy; however, whether the subiculum represents a site of ictogenesis for neonatal seizures remains unclear. In this study, multi-electrode recording techniques were used to record epileptiform discharges induced by low-Mg(2+) or high-K(+) artificial cerebrospinal fluid in neonatal mouse hippocampal slices, and the spatiotemporal dynamics of the epileptiform discharges were analyzed...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28469651/elevated-nkcc1-transporter-expression-facilitates-early-post-traumatic-brain-injury-seizures
#9
Buqing Liang, Jason H Huang
No abstract text is available yet for this article.
March 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28439270/cytokine-regulation-of-na-k-cl-cotransporter-1-and-cystic-fibrosis-transmembrane-conductance-regulator-potential-role-in-pulmonary-inflammation-and-edema-formation
#10
REVIEW
Sarah Weidenfeld, Wolfgang M Kuebler
Pulmonary edema, a major complication of lung injury and inflammation, is defined as accumulation of extravascular fluid in the lungs leading to impaired diffusion of respiratory gases. Lung fluid balance across the alveolar epithelial barrier protects the distal airspace from excess fluid accumulation and is mainly regulated by active sodium transport and Cl(-) absorption. Increased hydrostatic pressure as seen in cardiogenic edema or increased vascular permeability as present in inflammatory lung diseases such as the acute respiratory distress syndrome (ARDS) causes a reversal of transepithelial fluid transport resulting in the formation of pulmonary edema...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28438981/acute-inflammation-reveals-gabaa-receptor-mediated-nociception-in-mouse-dorsal-root-ganglion-neurons-via-pge2-receptor-4-signaling
#11
In Jeong Jang, Alexander J Davies, Nozomi Akimoto, Seung Keun Back, Pa Reum Lee, Heung Sik Na, Hidemasa Furue, Sung Jun Jung, Yong Ho Kim, Seog Bae Oh
Gamma-aminobutyric acid (GABA) depolarizes dorsal root ganglia (DRG) primary afferent neurons through activation of Cl(-) permeable GABAA receptors but the physiologic role of GABAA receptors in the peripheral terminals of DRG neurons remains unclear. In this study, we investigated the role of peripheral GABAA receptors in nociception using a mouse model of acute inflammation. In vivo, peripheral administration of the selective GABAA receptor agonist muscimol evoked spontaneous licking behavior, as well as spinal wide dynamic range (WDR) neuron firing, after pre-conditioning with formalin but had no effect in saline-treated mice...
April 2017: Physiological Reports
https://www.readbyqxmd.com/read/28433802/role-of-environmental-stressors-in-determining-the-developmental-outcome-of-neonatal-anesthesia
#12
Ling-Sha Ju, Jiao-Jiao Yang, Nikolaus Gravenstein, Christoph N Seubert, Timothy E Morey, Colin Sumners, Terrie Vasilopoulos, Jian-Jun Yang, Anatoly E Martynyuk
BACKGROUND: The majority of studies evaluating neurocognition in humans who had procedures under anesthesia early in life found long-term deficits even though the typical anesthesia duration normalized to the human life span is much shorter than that shown to induce developmental abnormalities in rodents. Therefore, we studied whether subsequent environmental stressors contribute to deficiencies programmed by a brief neonatal etomidate exposure. METHODS: Postnatal days (P) 4, 5, or 6, Sprague-Dawley rats, pretreated with vehicle or the Na(+)-K(+)-2Cl(-) (NKCC1) inhibitor, bumetanide, received two injections of etomidate resulting in anesthesia for 2h...
April 7, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28426550/neuropathic-pain-after-chronic-nerve-constriction-may-not-correlate-with-chloride-dysregulation-in-mouse-trigeminal-nucleus-caudalis-neurons
#13
Alberto Castro, Ying Li, Charles Raver, Ramesh Chandra, Radi Masri, Mary K Lobo, Asaf Keller
Changes in chloride reversal potential in rat spinal cord neurons have previously been associated with persistent pain in nerve injury and inflammation models. These changes correlate with a decrease in the expression of the potassium chloride transporter, KCC2, and with increases in neuronal excitability. Here, we test the hypothesis that similar changes occur in mice with neuropathic pain induced by chronic constriction injury of the trigeminal infraorbital nerve (CCI-ION). This model allows us to distinguish an acute pain phase (3-5 days after injury) from a persistent pain phase (12-14 days after CCI-ION)...
July 2017: Pain
https://www.readbyqxmd.com/read/28417963/loop-diuretics-affect-skeletal-myoblast-differentiation-and-exercise-induced-muscle-hypertrophy
#14
Shintaro Mandai, Susumu Furukawa, Manami Kodaka, Yutaka Hata, Takayasu Mori, Naohiro Nomura, Fumiaki Ando, Yutaro Mori, Daiei Takahashi, Yuki Yoshizaki, Yuri Kasagi, Yohei Arai, Emi Sasaki, Sayaka Yoshida, Yasuro Furuichi, Nobuharu L Fujii, Eisei Sohara, Tatemitsu Rai, Shinichi Uchida
Muscle wasting or sarcopenia contributes to morbidity and mortality in patients with cancer, renal failure, or heart failure, and in elderly individuals. Na(+)-K(+)-2Cl(-) cotransporter 1 (NKCC1) is highly expressed in mammalian skeletal muscle, where it contributes to the generation of membrane ion currents and potential. However, the physiologic function of NKCC1 in myogenesis is unclear. We investigated this issue using the NKCC1 inhibitors bumetanide and furosemide, which are commonly used loop diuretics...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28359949/establishment-of-lysozyme-gene-rna-interference-systemand-its-involvement-in-salinity-tolerance-in-sea-cucumber-apostichopus-japonicus
#15
Yi Tian, Yanan Jiang, Yanpeng Shang, Yu-Peng Zhang, Chen-Fan Geng, Li-Qiang Wang, Ya-Qing Chang
The lysozyme gene was silenced using RNA interference (RNAi) to analyze the function of lysozyme in sea cucumber under salt stress. The interfering efficiency of four lysozyme RNAi oligos ranged from 0.55 to 0.70. From the four oligos, p-miR-L245 was used for further interfering experiments because it had the best silencing efficiency. Peristomial film injection of p-miR-L245 (10 μg) was used for further interfering experiments. The lowest gene expression, determined by RT-PCR assay, in muscle, coelomic fluid, and parapodium occurred 48 h after p-miR-L245 injection, while that of body wall and tube foot was 96 h and 24 h, respectively...
March 28, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28344592/dysbindin-deficiency-modifies-the-expression-of-gaba-neuron-and-ion-permeation-transcripts-in-the-developing-hippocampus
#16
Jennifer Larimore, Stephanie A Zlatic, Miranda Arnold, Kaela S Singleton, Rebecca Cross, Hannah Rudolph, Martha V Bruegge, Andrea Sweetman, Cecilia Garza, Eli Whisnant, Victor Faundez
The neurodevelopmental factor dysbindin is required for synapse function and GABA interneuron development. Dysbindin protein levels are reduced in the hippocampus of schizophrenia patients. Mouse dysbindin genetic defects and other mouse models of neurodevelopmental disorders share defective GABAergic neurotransmission and, in several instances, a loss of parvalbumin-positive interneuron phenotypes. This suggests that mechanisms downstream of dysbindin deficiency, such as those affecting GABA interneurons, could inform pathways contributing to or ameliorating diverse neurodevelopmental disorders...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28337033/cortical-cells-reveal-app-as-a-new-player-in-the-regulation-of-gabaergic-neurotransmission
#17
Anna Doshina, Florian Gourgue, Michiho Onizuka, Remi Opsomer, Peng Wang, Kunie Ando, Bernadette Tasiaux, Ilse Dewachter, Pascal Kienlen-Campard, Jean-Pierre Brion, Philippe Gailly, Jean-Noël Octave, Nathalie Pierrot
The amyloid precursor protein (APP) modulates synaptic activity, resulting from the fine tuning of excitatory and inhibitory neurotransmission. GABAergic inhibitory neurotransmission is affected by modifications in intracellular chloride concentrations regulated by Na(+)-K(+)-2Cl(-) cotransporter 1 (NKCC1) and neuronal K(+)-Cl(-) cotransporter 2 (KCC2), allowing entrance and efflux of chloride, respectively. Modifications in NKCC1 and KCC2 expression during maturation of cortical cells induce a shift in GABAergic signaling...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28298895/two-phase-modulation-of-formula-see-text-entry-and-cl-formula-see-text-exchanger-in-submandibular-glands-cells-by-dexmedetomidine
#18
Minjeong Ji, Chul-Kyu Park, Jin Woo Lee, Kook Yang Park, Kuk Hui Son, Jeong Hee Hong
Dexmedetomidine (Dex), a highly selective α2-adrenoceptor agonist, attenuates inflammatory responses induced by lipopolysaccharide (LPS) and induces sedative and analgesic effects. Administration of Dex also reduces salivary secretion in human subjects and inhibits osmotic water permeability in rat cortical collecting ducts. However, little is known about the mechanisms underlying the effects of Dex on salivary glands fluid secretion. We demonstrated the α2-adrenoceptor expression in the basolateral membrane of mouse submandibular glands (SMG)...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28291262/effects-of-bumetanide-on-neurobehavioral-function-in-children-and-adolescents-with-autism-spectrum-disorders
#19
E Lemonnier, N Villeneuve, S Sonie, S Serret, A Rosier, M Roue, P Brosset, M Viellard, D Bernoux, S Rondeau, S Thummler, D Ravel, Y Ben-Ari
In animal models of autism spectrum disorder (ASD), the NKCC1 chloride-importer inhibitor bumetanide restores physiological (Cl(-))i levels, enhances GABAergic inhibition and attenuates electrical and behavioral symptoms of ASD. In an earlier phase 2 trial; bumetanide reduced the severity of ASD in children and adolescents (3-11 years old). Here we report the results of a multicenter phase 2B study primarily to assess dose/response and safety effects of bumetanide. Efficacy outcome measures included the Childhood Autism Rating Scale (CARS), the Social Responsive Scale (SRS) and the Clinical Global Impressions (CGI) Improvement scale (CGI-I)...
March 14, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28192112/multiple-blood-brain-barrier-transport-mechanisms-limit-bumetanide-accumulation-and-therapeutic-potential-in-the-mammalian-brain
#20
Kerstin Römermann, Maren Fedrowitz, Philip Hampel, Edith Kaczmarek, Kathrin Töllner, Thomas Erker, Douglas H Sweet, Wolfgang Löscher
There is accumulating evidence that bumetanide, which has been used over decades as a potent loop diuretic, also exerts effects on brain disorders, including autism, neonatal seizures, and epilepsy, which are not related to its effects on the kidney but rather mediated by inhibition of the neuronal Na-K-Cl cotransporter isoform NKCC1. However, following systemic administration, brain levels of bumetanide are typically below those needed to inhibit NKCC1, which critically limits its clinical use for treating brain disorders...
February 10, 2017: Neuropharmacology
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