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Chloride cotransporter

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https://www.readbyqxmd.com/read/28904232/effects-of-high-versus-moderate-intensity-training-on-neuroplasticity-and-functional-recovery-after-focal-ischemia
#1
Caroline Pin-Barre, Annabelle Constans, Jeanick Brisswalter, Christophe Pellegrino, Jérôme Laurin
BACKGROUND AND PURPOSE: This study was designed to compare the effects of high-intensity interval training (HIT) and moderate-intensity aerobic training (MOD) on functional recovery and cerebral plasticity during the first 2 weeks after cerebral ischemia. METHODS: Rats were randomized as follows: control (n=15), SHAM (n=9), middle cerebral artery occlusion (n=13), middle cerebral artery occlusion at day 1 (n=7), MOD (n=13), and HIT (n=13). Incremental tests were performed at day 1 (D1) and 14 (D14) to identify the running speed associated with the lactate threshold (SLT) and the maximal speed (Smax)...
September 13, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28888841/implications-of-the-n-terminal-heterogeneity-for-the-neuronal-k-cl-cotransporter-kcc2-function
#2
Marika Markkanen, Anastasia Ludwig, Stanislav Khirug, Evgeny Pryazhnikov, Shetal Soni, Leonard Khiroug, Eric Delpire, Claudio Rivera, Matti S Airaksinen, Pavel Uvarov
The neuron-specific K-Cl cotransporter KCC2 maintains the low intracellular chloride concentration required for the fast hyperpolarizing responses of the inhibitory neurotransmitters γ-aminobutyric acid (GABA) and glycine. The two KCC2 isoforms, KCC2a and KCC2b differ by their N-termini as a result of alternative promoter usage. Whereas the role of KCC2b in mediating the chloride transport is unequivocal, the physiological role of KCC2a in neurons has remained obscure. We show that KCC2a isoform can decrease the intracellular chloride concentration in cultured neurons and attenuate calcium responses evoked by application of the GABAA receptor agonist muscimol...
September 6, 2017: Brain Research
https://www.readbyqxmd.com/read/28885452/mirna-mediated-downregulation-of-kcc2-and-vgat-expression-in-spinal-cord-contributes-to-neonatal-cystitis-induced-visceral-pain-in-rats
#3
Jian Zhang, James Yu, Pradeep Kannampalli, Linghui Nie, Hui Meng, Bidyut Medda, Reza Shaker, Jyoti N Sengupta, Banani Banerjee
Loss of GABAergic inhibition in pain pathways has been considered to be a key component in the development of chronic pain. In the present study, we intended to examine if miR-92b-mediated post-transcriptional dysregulation of spinal potassium chloride cotransporter (KCC2) and vesicular GABA transporter (VGAT) plays a major role in the development and maintenance of long-term visceral hyperalgesia in neonatal zymosan-treated rats. Neonatal cystitis was induced by transurethral zymosan administration from postnatal (P) days 14-16 (protocol 1)...
September 1, 2017: Pain
https://www.readbyqxmd.com/read/28870047/-expert-consensus-for-the-diagnosis-and-treatment-of-patients-with-gitelman-syndrome
#4
(no author information available yet)
Gitelman syndrome (GS) is an autosomal recessive, salt-losing tubulopathy caused by inactivating mutations in the SLC12A3 gene that encodes the thiazide-sensitive sodium-chloride cotransporter (NCC). GS is characterized by hypokalemic metabolic alkalosis, hypomagnesemia and hypocalciuria. GS is one of the most common inherited renal tubulopathy with a prevalence estimated at about one to ten per 40 000 people. The prevalence of GS is even higher in Asia than other countries. The majority of GS patients present mild and nonspecific symptoms during adolescence or adulthood...
September 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/28860458/intracellular-chloride-regulation-in-avp-and-vip-neurons-of-the-suprachiasmatic-nucleus
#5
Nathan J Klett, Charles N Allen
Several reports have described excitatory GABA transmission in the suprachiasmatic nucleus (SCN), the master pacemaker of circadian physiology. However, there is disagreement regarding the prevalence, timing, and neuronal location of excitatory GABA transmission in the SCN. Whether GABA is inhibitory or excitatory depends, in part, on the intracellular concentration of chloride ([Cl(-)]i). Here, using ratiometric Cl(-) imaging, we have investigated intracellular chloride regulation in AVP and VIP-expressing SCN neurons and found evidence suggesting that [Cl(-)]i is higher during the day than during the night in both AVP+ and VIP+ neurons...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28844001/activation-of-5-ht2a-receptors-restores-kcc2-function-and-reduces-neuropathic-pain-after-spinal-cord-injury
#6
Irene Sánchez-Brualla, Pascale Boulenguez, Cécile Brocard, Sylvie Liabeuf, Annelise Viallat-Lieutaud, Xavier Navarro, Esther Udina, Frédéric Brocard
Downregulation of the potassium chloride cotransporter type 2 (KCC2) after a spinal cord injury (SCI) disinhibits motoneurons and dorsal horn interneurons causing spasticity and neuropathic pain, respectively. We showed recently (Bos et al., 2013) that specific activation of 5-HT2A receptors by TCB-2 [(4-bromo-3,6-dimethoxybenzocyclobuten-1-yl)methylamine hydrobromide] upregulates KCC2 function, restores motoneuronal inhibition and reduces SCI-induced spasticity. Here, we tested the potential analgesic effect of TCB-2 on central (thoracic hemisection) and peripheral [spared nerve injury (SNI)] neuropathic pain...
August 30, 2017: Neuroscience
https://www.readbyqxmd.com/read/28839192/indole-based-perenosins-as-highly-potent-hcl-transporters-and-potential-anti-cancer-agents
#7
Laura A Jowett, Ethan N W Howe, Vanessa Soto-Cerrato, Wim Van Rossom, Ricardo Pérez-Tomás, Philip A Gale
Prodigiosin is one of the most potent anion transporters in lipid bilayer membranes reported to date. Inspired by the structure of this natural product, we have recently designed and synthesised a new class of H(+)/Cl(-) cotransporters named 'perenosins'. Here we report a new library of indole-based perenosins and their anion transport properties. The new transporters demonstrated superior transmembrane transport efficiency when compared to other indole-based transporters, due to favourable encapsulating effects from the substituents on the perenosin backbone...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818393/the-modulation-of-the-phosphorylation-status-of-nkcc1-in-organ-cultured-bovine-lenses-implications-for-the-regulation-of-fiber-cell-and-overall-lens-volume
#8
Irene Vorontsova, Paul J Donaldson, Zhiying Kong, Chiharu Wickremesinghe, Leo Lam, Julie C Lim
In this study we have used an antibody that specifically detects the phosphorylation status of the Sodium/Potassium/2 Chloride Cotransporter (NKCC1) to study whether the activity of NKCC1 can be regulated in organ cultured bovine lenses. Western blotting was first used to confirm the expression of NKCC1, phosphorylated NKCC1 (NKCC1-P) and the regulatory kinases WNK/SPAK and phosphatases PP1/PP2A in bovine lenses at the protein level. Changes to NKCC1-P status were then assessed by organ culturing bovine lenses in either isotonic, hypertonic or hypotonic solutions in the presence or absence of the NKCC inhibitor, bumetanide, or phosphatase inhibitors okadaic acid and calyculin A...
August 14, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28803659/seizing-control-of-kcc2-a-new-therapeutic-target-for-epilepsy
#9
REVIEW
Yvonne E Moore, Matt R Kelley, Nicholas J Brandon, Tarek Z Deeb, Stephen J Moss
Deficits in GABAergic inhibition result in the abnormal neuronal activation and synchronization that underlies seizures. However, the molecular mechanisms responsible for transforming a normal brain into an epileptic one remain largely unknown. Hyperpolarizing inhibition mediated by type A GABA (GABAA) receptors is dependent on chloride extrusion by the neuron-specific type 2K(+)-Cl(-) cotransporter (KCC2). Loss-of-function mutations in KCC2 are a known cause of infantile epilepsy in humans and KCC2 dysfunction is present in patients with both idiopathic and acquired epilepsy...
August 10, 2017: Trends in Neurosciences
https://www.readbyqxmd.com/read/28796813/a-novel-organotypic-3d-sweat-gland-model-with-physiological-functionality
#10
Patricia Klaka, Sabine Grüdl, Bernhard Banowski, Melanie Giesen, Andrea Sättler, Peter Proksch, Thomas Welss, Thomas Förster
Dysregulated human eccrine sweat glands can negatively impact the quality-of-life of people suffering from disorders like hyperhidrosis. Inability of sweating can even result in serious health effects in humans affected by anhidrosis. The underlying mechanisms must be elucidated and a reliable in vitro test system for drug screening must be developed. Here we describe a novel organotypic three-dimensional (3D) sweat gland model made of primary human eccrine sweat gland cells. Initial experiments revealed that eccrine sweat gland cells in a two-dimensional (2D) culture lose typical physiological markers...
2017: PloS One
https://www.readbyqxmd.com/read/28782830/altered-behavioral-responses-to-gamma-aminobutyric-acid-pharmacological-agents-in-a-mouse-model-of-huntington-s-disease
#11
Yi-Ting Hsu, Ya-Gin Chang, Ching-Pang Chang, Jian-Jing Siew, Hui-Mei Chen, Chon-Haw Tsai, Yijuang Chern
BACKGROUND: Disruptions in gamma-aminobutyric (GABA) acid signaling are believed to be involved in Huntington's disease pathogenesis, but the regulation of GABAergic signaling remains elusive. Here we evaluated GABAergic signaling by examining the function of GABAergic drugs in Huntington's disease and the expression of GABAergic molecules using mouse models and human brain tissues from Huntington's disease. METHODS: We treated wild-type and R6/2 mice (a transgenic Huntington's disease mouse model) acutely with vehicle, diazepam, or gaboxadol (drugs that selectively target synaptic or extrasynaptic GABAA receptors) and monitored their locomotor activity...
August 7, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28762276/synthesis-of-aryl-c-glycosides-via-iron-catalyzed-cross-coupling-of-halosugars-stereoselective-anomeric-arylation-of-glycosyl-radicals
#12
Laksmikanta Adak, Shintaro Kawamura, Gabriel Toma, Toshio Takenaka, Katsuhiro Isozaki, Hikaru Takaya, Akihiro Orita, Ho C Li, Tony K M Shing, Masaharu Nakamura
We have developed a novel diastereoselective iron-catalyzed cross-coupling reaction of various glycosyl halides with aryl metal reagents for the efficient synthesis of aryl C-glycosides, which are of significant pharmaceutical interest due to their biological activities and resistance toward metabolic degradation. A variety of aryl, heteroaryl, and vinyl metal reagents can be cross-coupled with glycosyl halides in high yields in the presence of a well-defined iron complex, composed of iron(II) chloride and a bulky bisphosphine ligand, TMS-SciOPP...
August 1, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28759755/the-roles-of-sodium-glucose-cotransporter-2-inhibitors-in-preventing-kidney-injury-in-diabetes
#13
REVIEW
Krit Jaikumkao, Anchalee Pongchaidecha, Varanuj Chatsudthipong, Siriporn C Chattipakorn, Nipon Chattipakorn, Anusorn Lungkaphin
Diabetic nephropathy (DN) is the leading cause of end stage renal disease (ESRD) worldwide. The early effective treatment of high plasma glucose could delay or prevent the onset of DN. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are new target treatments for ameliorating high plasma glucose and help to maintain glucose homeostasis in diabetic patients. Reduced renal glucose reabsorption by SGLT2 inhibition seems to have high potential to improve glycemic control in diabetes mellitus (DM) not only through glucose lowering but also through glucose-independent effects such as blood pressure-lowering and direct renal effects in diabetes...
July 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28750403/ablation-of-the-cl-hco3-exchanger-pendrin-enhances-hydrochlorothiazide-induced-diuresis
#14
Saeed Alshahrani, Manoocher Soleimani
BACKGROUND/AIMS: The Cl-/HCO3- exchanger pendrin and the thiazide-sensitive Na-Cl cotransporter NCC are expressed in the kidney distal nephron and mediate salt absorption. We hypothesized that deletion of pendrin leaves NCC as the major salt absorbing transporter in the distal nephron and therefore enhances salt excretion by hydrochlorothiazide (HCTZ). METHODS: Metabolic cage studies were performed in wild type, pendrin KO and NCC KO mice at baseline and following HCTZ treatment...
July 27, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/28744758/gitelman-syndrome-an-analysis-of-the-underlying-pathophysiologic-mechanisms-of-acid-base-and-electrolyte-abnormalities
#15
REVIEW
T D Filippatos, C V Rizos, E Tzavella, M S Elisaf
Gitelman syndrome is the most common inherited tubular disease resulting from mutations of the SLC12A3 gene that encodes the thiazide-sensitive sodium-chloride cotransporter in the early distal convoluted tubules. The review presents the underlying pathophysiologic mechanisms of acid-base and electrolyte abnormalities observed in patients with Gitelman syndrome. The syndrome is usually characterized by hypokalemic metabolic alkalosis in combination with hypomagnesemia and hypocalciuria. Additionally, increased chloride excretion and renin/aldosterone levels, hypophosphatemia (occasionally), hyponatremia (rarely) and glucose intolerance/insulin resistance have been reported...
July 25, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28677029/the-role-of-k-cl-cotransporter-2-in-neuropathic-pain
#16
Tomoya Kitayama
The pain sensory system normally functions under a fine balance between excitation and inhibition. When this balance is perturbed for some reason, it leads to neuropathic pain. There is accumulating evidence that attributes this pain generation to specific dysfunctions of the inhibitory system in the spinal cord. One possible mechanism leading to the induction of these dysfunctions is the down-regulation of K(+)-Cl(-)-cotransporter-2 (KCC2) expression. In fact, various neuropathic pain models indicate a decrease of KCC2 expression in the spinal cord...
July 4, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28662098/molecular-cloning-and-biochemical-characterization-of-two-cation-chloride-cotransporter-subfamily-members-of-hydra-vulgaris
#17
Anna-Maria Hartmann, Lucie I Pisella, Igor Medina, Hans Gerd Nothwang
Cation Chloride Cotransporters (CCCs) comprise secondary active membrane proteins mainly mediating the symport of cations (Na+, K+) coupled with chloride (Cl-). They are divided into K+-Cl- outward transporters (KCCs), the Na+-K+-Cl- (NKCCs) and Na+-Cl- (NCCs) inward transporters, the cation chloride cotransporter interacting protein CIP1, and the polyamine transporter CCC9. KCCs and N(K)CCs are established in the genome since eukaryotes and metazoans, respectively. Most of the physiological and functional data were obtained from vertebrate species...
2017: PloS One
https://www.readbyqxmd.com/read/28651800/cellular-mechanisms-underlying-the-inhibitory-effect-of-flufenamic-acid-on-chloride-secretion-in-human-intestinal-epithelial-cells
#18
Pawin Pongkorpsakol, Chantapol Yimnual, Varanuj Chatsudthipong, Vatcharin Rukachaisirikul, Chatchai Muanprasat
Intestinal Cl(-) secretion is involved in the pathogenesis of secretory diarrheas including cholera. We recently demonstrated that flufenamic acid (FFA) suppressed Vibriocholerae El Tor variant-induced intestinal fluid secretion via mechanisms involving AMPK activation and NF-κB-suppression. The present study aimed to investigate the effect of FFA on transepithelial Cl(-) secretion in human intestinal epithelial (T84) cells. FFA inhibited cAMP-dependent Cl(-) secretion in T84 cell monolayers with IC50 of ∼8 μM...
June 10, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28647557/kcc3-loss-of-function-contributes-to-andermann-syndrome-by-inducing-activity-dependent-neuromuscular-junction-defects
#19
Melissa Bowerman, Céline Salsac, Véronique Bernard, Claire Soulard, Annie Dionne, Emmanuelle Coque, Salim Benlefki, Pascale Hince, Patrick A Dion, Gillian Butler-Browne, William Camu, Jean-Pierre Bouchard, Eric Delpire, Guy A Rouleau, Cédric Raoul, Frédérique Scamps
Loss-of-function mutations in the potassium-chloride cotransporter KCC3 lead to Andermann syndrome, a severe sensorimotor neuropathy characterized by areflexia, amyotrophy and locomotor abnormalities. The molecular events responsible for axonal loss remain poorly understood. Here, we establish that global or neuron-specific KCC3 loss-of-function in mice leads to early neuromuscular junction (NMJ) abnormalities and muscular atrophy that are consistent with the pre-synaptic neurotransmission defects observed in patients...
June 21, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28646163/aldosterone-modulates-the-association-between-ncc-and-enac
#20
Brandi M Wynne, Abinash C Mistry, Otor Al-Khalili, Rickta Mallick, Franziska Theilig, Douglas C Eaton, Robert S Hoover
Distal sodium transport is a final step in the regulation of blood pressure. As such, understanding how the two main sodium transport proteins, the thiazide-sensitive sodium chloride cotransporter (NCC) and the epithelial sodium channel (ENaC), are regulated is paramount. Both are expressed in the late distal nephron; however, no evidence has suggested that these two sodium transport proteins interact. Recently, we established that these two sodium transport proteins functionally interact in the second part of the distal nephron (DCT2)...
June 23, 2017: Scientific Reports
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