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Chloride cotransporter

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https://www.readbyqxmd.com/read/29146941/developmental-excitatory-to-inhibitory-gaba-polarity-switch-is-disrupted-in-22q11-2-deletion-syndrome-a-potential-target-for-clinical-therapeutics
#1
Hayder Amin, Federica Marinaro, Davide De Pietri Tonelli, Luca Berdondini
Individuals with 22q11.2 microdeletion syndrome (22q11.2 DS) show cognitive and behavioral dysfunctions, developmental delays in childhood and risk of developing schizophrenia and autism. Despite extensive previous studies in adult animal models, a possible embryonic root of this syndrome has not been determined. Here, in neurons from a 22q11.2 DS mouse model (Lgdel (+/-)), we found embryonic-premature alterations in the neuronal chloride cotransporters indicated by dysregulated NKCC1 and KCC2 protein expression levels...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29131070/pathophysiology-of-post-transplant-hypertension-in-kidney-transplant-focus-on-calcineurin-inhibitors-induced-oxidative-stress-and-renal-sodium-retention-and-implications-with-rhoa-rho-kinase-pathway
#2
Lorenzo A Calò, Verdiana Ravarotto, Francesca Simioni, Elena Naso, Francesco Marchini, Luciana Bonfante, Lucrezia Furian, Paolo Rigotti
Post-transplant hypertension is a common occurrence during treatment with calcineurin inhibitors (CNIs) in kidney transplant population. The pathogenesis of vasoconstriction induced by CNIs involves vascular tone alterations and kidney sodium transport regulation. Among the factors involved a key role is played by the activation of intrarenal renin-angiotensin system with enhanced release of Angiotensin II (Ang II) and increase of oxidative stress. A common pathway between oxidative stress and hypertension induced by CNIs may be identified in the involvement of the activation of RhoA/Rho kinase pathway, key for the induction of hypertension and cardiovascular-renal remodeling, of the oxidative stress mediated increased nitric oxide (NO) metabolism and increased renal sodium retention via increased activity of thiazide-sensitive sodium chloride cotransporter (NCC) in the distal tubule...
October 16, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29126251/evidence-for-a-role-of-pdz-domain-containing-proteins-to-mediate-hypophosphatemia-in-calcium-stone-formers
#3
Kristin J Bergsland, Fredric L Coe, Joan H Parks, John R Asplin, Elaine M Worcester
Background: Hypophosphatemia (HYP) is common among calcium stone formers (SFs) and in rare cases is associated with mutations in sodium-phosphate cotransporters or in Na+/H+ exchanger regulatory factor 1 (NHERF1), but the majority of cases are unexplained. We hypothesized that reduced sodium-phosphate cotransporter activity mediated via NHERF1 or a similar PDZ domain-containing protein, causes HYP. If so, other transport activities controlled by NHERF1, such as NHE3 and URAT1, might be reduced in HYP...
November 6, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29120956/protein-kinase-c%C3%AE-deletion-causes-hypotension-and-decreased-vascular-contractility
#4
Brandi M Wynne, Cameron G McCarthy, Theodora Szasz, Patrick A Molina, Arlene B Chapman, R Clinton Webb, Janet D Klein, Robert S Hoover
AIM: Protein kinase Cα (PKCα) is a critical regulator of multiple cell signaling pathways including gene transcription, posttranslation modifications and activation/inhibition of many signaling kinases. In regards to the control of blood pressure, PKCα causes increased vascular smooth muscle contractility, while reducing cardiac contractility. In addition, PKCα has been shown to modulate nephron ion transport. However, the role of PKCα in modulating mean arterial pressure (MAP) has not been investigated...
November 8, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/29066461/inactivation-of-spak-kinase-reduces-body-weight-gain-in-mice-fed-a-high-fat-diet-by-improving-energy-expenditure-and-insulin-sensitivity
#5
Ivan Torre-Villalvazo, Luz Graciela Cervantes-Perez, Lilia G Noriega, Jose V Jimenez, Norma Uribe, Maria Chavez-Canales, Claudia Tovar-Palacio, Braulio A Marfil-Garza, Nimbe Torres, Norma A Bobadilla, Armando R Tovar, Gerardo Gamba
The STE20/SPS1-related proline-alanine-rich protein kinase (SPAK) controls the activity of the electroneutral cation-chloride cotransporters (SLC12 family) and thus physiological processes such as modulation of cell volume, intracellular chloride concentration [Cl-]i and transepithelial salt transport. Modulation of SPAK kinase activity may have an impact on hypertension and obesity as STK39, the gene encoding SPAK has been suggested as a hypertension and obesity susceptibility gene. In fact, the absence of SPAK activity in mice in which the activating threonine in the T-loop was substituted by alanine (SPAK-KI mice) is associated with decreased blood pressure; however its consequences in metabolism have not been explored...
October 24, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29058295/effects-of-high-frequency-repetitive-transcranial-magnetic-stimulation-on-kcc2-expression-in-rats-with-spasticity-following-spinal-cord-injury
#6
Wei Gao, Li-Guo Yu, Ya-Li Liu, Mo Chen, Yi-Zhao Wang, Xiao-Lin Huang
The effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) on potassium- chloride cotransporter-2 (KCC2) protein expression following spinal cord injury (SCI) and the action mechanism were investigated. SCI models were established in SD rats. Five groups were set up randomly: normal control group, SCI 7-day (7D) model group, SCI 14-day (14D) model group, SCI-7D rTMS group and SCI-14D rTMS group (n=5 each). The rats in SCI rTMS groups were treated with 10 Hz rTMS from 8th day and 15th day after SCI respectively, once every day, 5 days every week, a total of 4 weeks...
October 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/29029515/discovery-of-nkcc1-as-a-potential-therapeutic-target-to-inhibit-hepatocellular-carcinoma-cell-growth-and-metastasis
#7
Yaya Zhou, Wei Sun, Ning Chen, Chen Xu, Xinxin Wang, Kun Dong, Binxue Zhang, Jian Zhang, Ning Hao, Aihua Sun, Handong Wei, Fuchu He, Ying Jiang
Metastasis is the essential cause for the high mortality of hepatocellular carcinoma (HCC). In order to investigate the mechanism of metastasis, and to discover therapeutic targets for HCC, the quantitative proteomic technique was applied to characterize the plasma membrane proteins of two HCC cell lines with low (MHCC97L) or high (MHCC97H) metastatic potentials. One of the plasma membrane proteins, sodium-potassium-chloride cotransporter 1 (NKCC1), was upregulated in MHCC97H cell line. Immunohistochemistry result in HCC patients showed that NKCC1 expression was associated with poor differentiation and microvascular invasion...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29021560/the-thiazide-sensitive-sodium-chloride-co-transporter-ncc-is-modulated-by-site-specific-ubiquitylation
#8
Lena L Rosenbaek, Federica Rizzo, Qi Wu, Lorena Rojas-Vega, Gerardo Gamba, Nanna MacAulay, Olivier Staub, Robert A Fenton
The renal sodium chloride cotransporter, NCC, in the distal convoluted tubule is important for maintaining body Na(+) and K(+) homeostasis. Endogenous NCC is highly ubiquitylated, but the role of individual ubiquitylation sites is not established. Here, we assessed the role of 10 ubiquitylation sites for NCC function. Transient transfections of HEK293 cells with human wildtype (WT) NCC or various K to R mutants identified greater membrane abundance for K706R, K828R and K909R mutants. Relative to WT-NCC, stable tetracycline inducible MDCKI cell lines expressing K706R, K828R and K909R mutants had significantly higher total and phosphorylated NCC levels at the apical plasma membrane under basal conditions...
October 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28973889/simultaneous-two-photon-imaging-of-intracellular-chloride-concentration-and-ph-in-mouse-pyramidal-neurons-in-vivo
#9
Sebastian Sulis Sato, Pietro Artoni, Silvia Landi, Olga Cozzolino, Riccardo Parra, Enrico Pracucci, Francesco Trovato, Joanna Szczurkowska, Stefano Luin, Daniele Arosio, Fabio Beltram, Laura Cancedda, Kai Kaila, Gian Michele Ratto
Intracellular chloride ([Cl(-)]i) and pH (pHi) are fundamental regulators of neuronal excitability. They exert wide-ranging effects on synaptic signaling and plasticity and on development and disorders of the brain. The ideal technique to elucidate the underlying ionic mechanisms is quantitative and combined two-photon imaging of [Cl(-)]i and pHi, but this has never been performed at the cellular level in vivo. Here, by using a genetically encoded fluorescent sensor that includes a spectroscopic reference (an element insensitive to Cl(-) and pH), we show that ratiometric imaging is strongly affected by the optical properties of the brain...
October 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28935959/the-crystal-structure-of-the-regulatory-domain-of-the-human-sodium-driven-chloride-bicarbonate-exchanger
#10
Carolina M Alvadia, Theis Sommer, Kaare Bjerregaard-Andersen, Helle Hasager Damkier, Michele Montrasio, Christian Aalkjaer, J Preben Morth
The sodium-driven chloride/bicarbonate exchanger (NDCBE) is essential for maintaining homeostatic pH in neurons. The crystal structure at 2.8 Å resolution of the regulatory N-terminal domain of human NDCBE represents the first crystal structure of an electroneutral sodium-bicarbonate cotransporter. The crystal structure forms an equivalent dimeric interface as observed for the cytoplasmic domain of Band 3, and thus establishes that the consensus motif VTVLP is the key minimal dimerization motif. The VTVLP motif is highly conserved and likely to be the physiologically relevant interface for all other members of the SLC4 family...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28923771/differential-expression-of-putative-sodium-dependent-cation-chloride-cotransporters-in-aedes-aegypti
#11
Peter M Piermarini, Daniel C Akuma, John C Crow, Taylor L Jamil, Willa G Kerkhoff, Kenyatta C M F Viel, Christopher M Gillen
The yellow fever mosquito, Aedes aegypti, has three genes that code for proteins with sequence similarity to vertebrate Na(+)-K(+)-Cl(-) cotransporters (NKCCs) of the solute-linked carrier 12 superfamily of cation-chloride cotransporters (CCCs). We hypothesized that these mosquito NKCC orthologues have diverged to perform distinct roles in salt secretion and absorption. In phylogenetic analyses, one protein (aeNKCC1) groups with a Drosophila melanogaster NKCC that mediates salt secretion whereas two others (aeCCC2 and aeCCC3) group with a Drosophila transporter that is not functionally characterized...
December 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/28904232/effects-of-high-versus-moderate-intensity-training-on-neuroplasticity-and-functional-recovery-after-focal-ischemia
#12
COMPARATIVE STUDY
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)...
October 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
#13
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...
November 15, 2017: Brain Research
https://www.readbyqxmd.com/read/28885452/microrna-mediated-downregulation-of-potassium-chloride-cotransporter-and-vesicular-%C3%AE-aminobutyric-acid-transporter-expression-in-spinal-cord-contributes-to-neonatal-cystitis-induced-visceral-pain-in-rats
#14
Jian Zhang, James Yu, Pradeep Kannampalli, Linghui Nie, Hui Meng, Bidyut K 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 whether miR-92b-mediated posttranscriptional dysregulation of spinal potassium chloride cotransporter (KCC2) and vesicular γ-aminobutyric acid 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 to 16 (protocol 1)...
December 2017: Pain
https://www.readbyqxmd.com/read/28870047/-expert-consensus-for-the-diagnosis-and-treatment-of-patients-with-gitelman-syndrome
#15
(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
#16
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
#17
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
#18
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
#19
Irene Vorontsova, Paul J Donaldson, Zhiying Kong, Chiharu Wickremesinghe, Leo Lam, Julie C Lim
In previous work, we have shown the Sodium/Potassium/2 Chloride Cotransporter (NKCC1) to be a key effector of lens fiber cell volume regulation. Since others have shown that the activity of NKCC1 is regulated via its phosphorylation status, the purpose of this study was to investigate whether NKCC1 phosphorylation can be modulated in organ cultured bovine lenses, and to see how this relates to changes in lens wet weight. 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...
August 14, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28803659/seizing-control-of-kcc2-a-new-therapeutic-target-for-epilepsy
#20
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
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