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calcium channel pumps

Chao Chen, Susana Gardete, Robert Sander Jansen, Annanya Shetty, Thomas Dick, Kyu Y Rhee, Véronique Dartois
Mycobacterium tuberculosis (Mtb) kills more people than any other bacterial pathogen and is becoming increasingly untreatable due to the emergence of resistance. Verapamil, an FDA-approved calcium channel blocker, potentiates the effect of several anti-tuberculosis (TB) drugs in vitro and in vivo. This potentiation is widely attributed to inhibition of Mtb's efflux pumps, resulting in intrabacterial drug accumulation. Here, we confirm and quantify verapamil's synergy with several anti-TB drugs, including bedaquiline and clofazimine, but find that this effect is not due to increased intrabacterial drug accumulation...
February 20, 2018: Antimicrobial Agents and Chemotherapy
Parvana Hajieva, Marius W Baeken, Bernd Moosmann
Selective degeneration of differentiated neurons in the brain is the unifying feature of neurodegenerative disorders such as Parkinson's disease (PD) or Alzheimer's disease (AD). A broad spectrum of evidence indicates that initially subtle, but temporally early calcium dysregulation may be central to the selective neuronal vulnerability observed in these slowly progressing, chronic disorders. Moreover, it has long been evident that excitotoxicity and its major toxic effector mechanism, neuronal calcium overload, play a decisive role in the propagation of secondary neuronal death after acute brain injury from trauma or ischemia...
January 10, 2018: Neuroscience Letters
Mario Bortolozzi, Fabio Mammano
Hair cells of the inner ear detect sound stimuli, inertial or gravitational forces by deflection of their apical stereocilia. A small number of stereociliary cation-selective mechanotransduction (MET) channels admit K+ and Ca2+ ions into the cytoplasm promoting hair cell membrane depolarization and, consequently, neurotransmitter release at the cell basolateral pole. Ca2+ influx into the stereocilia compartment is counteracted by the unusual w/a splicing variant of plasma-membrane calcium-pump isoform 2 (PMCA2) which, unlike other PMCA2 variants, increases only marginally its activity in response to a rapid variation of the cytoplasmic free Ca2+ concentration ([Ca2+ ]c )...
January 10, 2018: Neuroscience Letters
Xinghua Feng, Zhuangzhuang Zhao, Qian Li, Zhiyong Tan
The lysosome is a membrane-enclosed organelle widely found in every eukaryotic cell. It has been deemed as the stomach of the cells. Recent studies revealed that it also functions as an intracellular calcium store and is a platform for nutrient-dependent signal transduction. Similar with the plasma membrane, the lysosome membrane is furnished with various proteins, including pumps, ion channels and transporters. So far, two types of lysosomal potassium channels have been identified: large-conductance and Ca2+-activated potassium channel (BK) and TMEM175...
February 1, 2018: CNS & Neurological Disorders Drug Targets
Iman Azimi
The interplay between hypoxia-inducible factor-1 (HIF-1) and calcium in cancer has begun to be unravelled with recent findings demonstrating the relationships between the two in different cancer types. This is an area of significance considering the crucial roles of both HIF-1 and calcium signalling in cancer progression and metastasis. This review summarises the experimental evidence of the crosstalk between HIF-1 and specific calcium channels, pumps and regulators in the context of cancer. HIF-1 as a master regulator of hypoxic transcriptional responses, mediates transcription of several calcium modulators...
February 3, 2018: International Journal of Biochemistry & Cell Biology
Scott D Zawieja, Jorge A Castorena-Gonzalez, Joshua Scallan, Michael J Davis
We identified a regional dichotomy in murine lymphatic contractile function with regard to vessel location within either the periphery or visceral cavity. All vessels isolated from peripheral regions; cervical, popliteal, inguinal, axillary, and inter-nodal inguinal axillary (Ing-Ax) developed robust contractions with maximal ejection fractions (EFs) of 50-80% in our ex vivo isobaric myograph experiments. Conversely, vessels isolated from the visceral cavity (mesenteric, TD, and iliac) demonstrated maximal EFs below 15%...
January 5, 2018: American Journal of Physiology. Heart and Circulatory Physiology
Richmond Muimo, Hani Mm Alothaid, Anil Mehta
NM23 proteins NDPK-A and -B bind to the cystic fibrosis (CF) protein CFTR in different ways from kinases such as PKA, CK2 and AMPK or linkers to cell calcium such as calmodulin and annexins. NDPK-A (not -B) interacts with CFTR through reciprocal AMPK binding/control, whereas NDPK-B (not -A) binds directly to CFTR. NDPK-B can activate G proteins without ligand-receptor coupling, so perhaps NDPK-B's binding influences energy supply local to a nucleotide-binding site (NBD1) needed for CFTR to function. Curiously, CFTR (ABC-C7) is a member of the ATP-binding cassette (ABC) protein family that does not obey 'clan rules'; CFTR channels anions and is not a pump, regulates disparate processes, is itself regulated by multiple means and is so pleiotropic that it acts as a hub that orchestrates calcium signaling through its consorts such as calmodulin/annexins...
December 18, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
Marianela G Dalghi, Mariela Ferreira-Gomes, Juan Pablo Rossi
Associations between the cortical cytoskeleton and the components of the plasma membrane are no longer considered to be merely of structural and mechanical nature but are nowadays recognized as dynamic interactions that modulate a plethora of cellular responses. Reorganization of actin filaments upon diverse stimuli - among which is the rise in cytosolic Ca2+ - is involved in cell motility and adhesion, phagocytosis, cytokinesis, and secretion. Actin dynamics also participates in the regulation of ion transport across the membranes where it not only plays a key role in the delivery and stabilization of channels and transporters in the plasma membrane but also in the regulation of their activity...
November 24, 2017: Biochemical and Biophysical Research Communications
Romain Helleringer, Oana Chever, Hervé Daniel, Micaela Galante
During brain ischemia, intense energy deficiency induces a complex succession of events including pump failure, acidosis and exacerbated glutamate release. In the cerebellum, glutamate is the principal mediator of Purkinje neuron anoxic depolarization during episodes of oxygen and glucose deprivation (OGD). Here, the impact of OGD is studied in Bergmann glia, specialized astrocytes closely associated to Purkinje neurons. Patch clamp experiments reveal that during OGD Bergmann glial cells develop a large depolarizing current that is not mediated by glutamate and purinergic receptors but is mainly due to the accumulation of K+ in the extracellular space...
2017: Frontiers in Cellular Neuroscience
Michelle Flores Domingues, Dênis Reis de Assis, Angela Regina Piovesan, Cháriston André Dal Belo, Jaderson Costa da Costa
Peptide YY (PYY) belongs to the neuropeptide Y (NPY) family, which also includes the pancreatic polypeptide (PP) and NPY. PYY is secreted by the intestinal L cells, being present in the blood stream in two active forms capable of crossing the blood brain barrier, PYY (1-36) and its cleavage product, PYY (3-36). PYY is a selective agonist for the Y2 receptor (Y2R) and these receptors are abundant in the hippocampus. Here we investigated the mechanisms by which PYY (3-36) regulates intracellular Ca(2+) concentrations ([Ca(2+)]i) in hippocampal neurons by employing a calcium imaging technique in hippocampal cultures...
November 7, 2017: Neuropeptides
Amir Tajbakhsh, Alireza Pasdar, Mehdi Rezaee, Mostafa Fazeli, Saman Soleimanpour, Seyed Mahdi Hassanian, Zahra FarshchiyanYazdi, Tayebe Younesi Rad, Gordon A Ferns, Amir Avan
Calcium ions (Ca2+ ) act as second messengers in intracellular signaling. Ca2+ pumps, channels, sensors, and calcium binding proteins, regulate the concentrations of intracellular Ca2+ as a key regulator of important cellular processes such as gene expression, proliferation, differentiation, DNA repair, apoptosis, metastasis, and hormone secretion. Intracellular Ca2+ also influences the functions of several organelles, that include: the endoplasmic reticulum, mitochondria, the Golgi, and cell membrane both in normal and breast cancer cells...
November 18, 2017: Journal of Cellular Physiology
Akira Onodera, Katsutoshi Yayama, Hideto Morosawa, Yukina Ishii, Yasuo Tsutsumi, Yuichi Kawai
Several studies have reported that amorphous nano-silica particles (nano-SPs) modulate calcium flux, although the mechanism remains incompletely understood. We thus analyzed the relationship between calcium flux and particle surface properties and determined the calcium flux route. Treatment of Balb/c 3T3 fibroblasts with nano-SPs with a diameter of 70 nm (nSP70) increased cytosolic calcium concentration, but that with SPs with a diameter of 300 or 1000 nm did not. Surface modification of nSP70 with a carboxy group also did not modulate calcium flux...
March 2017: Biochemistry and Biophysics Reports
Yu Guan, Daisuke Nakano, Yifan Zhang, Lei Li, Wenhua Liu, Motohiro Nishida, Takashige Kuwabara, Asahiro Morishita, Hirofumi Hitomi, Kiyoshi Mori, Masashi Mukoyama, Tsutomu Masaki, Katsuya Hirano, Akira Nishiyama
The kidney expresses protease-activated receptor-1 (PAR-1). PAR-1 is known as a thrombin receptor, but its role in kidney injury is not well understood. In this study, we examined the contribution of PAR-1 to kidney glomerular injury and the effects of its inhibition on development of nephropathy. Mice were divided into 3 groups: control, doxorubicin + vehicle (15 mg/kg doxorubicin and saline) and doxorubicin + Q94 (doxorubicin at 15 mg/kg and the PAR-1 antagonist Q94 at 5 mg/kg/d) groups. Where indicated, doxorubicin was administered intravenously and PAR-1 antagonist or saline vehicle by subcutaneous osmotic mini-pump...
September 14, 2017: Journal of Pharmacological Sciences
Derek T A Lamport, Li Tan, Michael A Held, Marcia J Kieliszewski
Occam's Razor suggests a new model of pollen tube tip growth based on a novel Hechtian oscillator that integrates a periplasmic arabinogalactan glycoprotein-calcium (AGP-Ca2+ ) capacitor with tip-localized AGPs as the source of tip-focussed cytosolic Ca2+ oscillations: Hechtian adhesion between the plasma membrane and the cell wall of the growing tip acts as a piconewton force transducer that couples the internal stress of a rapidly growing wall to the plasma membrane. Such Hechtian transduction opens stretch-activated Ca2+ channels and activates H+ -ATPase proton pump efflux that dissociates periplasmic AGP-Ca2+ resulting in a Ca2+ influx that activates exocytosis of wall precursors...
January 2018: New Phytologist
Hemant Kumar Gupta, Shruti Shrivastava, Rakesh Sharma
Ca(2+) plays an important role in the physiology of bacteria. Intracellular Ca(2+) concentrations are tightly maintained in the nanomolar range. Molecular mechanisms of Ca(2+) uptake in bacteria remain elusive. Here we show that CtpE is responsible for Ca(2+) uptake in Mycobacterium smegmatis It represents a previously uncharacterized P-type ATPase family in bacteria. Disruption of ctpE in M. smegmatis resulted in a mutant with impaired growth under Ca(2+)-deficient conditions. The growth defect of the mutant could be rescued by Ca(2+) or by ectopic expression of ctpE from M...
September 26, 2017: MBio
Martin D Bootman, Katja Rietdorf
Calcium (Ca2+ ) is a key regulator of cardiomyocyte contraction. The Ca2+ channels, pumps, and exchangers responsible for the cyclical cytosolic Ca2+ signals that underlie contraction are well known. In addition to those Ca2+ signaling components responsible for contraction, it has been proposed that cardiomyocytes express channels that promote the influx of Ca2+ from the extracellular milieu to the cytosol in response to depletion of intracellular Ca2+ stores. With non-excitable cells, this store-operated Ca2+ entry (SOCE) is usually easily demonstrated and is essential for prolonging cellular Ca2+ signaling and for refilling depleted Ca2+ stores...
2017: Advances in Experimental Medicine and Biology
Mona Suryana, Jegan V Shanmugarajah, Sivakumar M Maniam, Gianluca Grenci
Infrared (IR) spectro-microscopy of living biological samples is hampered by the absorption of water in the mid-IR range and by the lack of suitable microfluidic devices. Here, a protocol for the fabrication of plastic microfluidic devices is demonstrated, where soft lithographic techniques are used to embed transparent Calcium Fluoride (CaF2) view-ports in connection with observation chamber(s). The method is based on a replica casting approach, where a polydimethylsiloxane (PDMS) mold is produced through standard lithographic procedures and then used as the template to produce a plastic device...
August 17, 2017: Journal of Visualized Experiments: JoVE
Phonindra Nath Das, Ajay Kumar, Nandadulal Bairagi, Samrat Chatterjee
Calcium homeostasis is a key factor in the regulation of cardiac excitation-contraction coupling. Calcium dynamics in cardiomyocytes is governed by ATP which depends on insulin dependent glucose concentration, via the glucose transporter type 4 (GLUT4) transporter. It would therefore be interesting to see how calcium dynamics changes in a cardiomyocyte under diabetic conditions. We proposed and analysed a four dimensional ordinary differential equation (ODE) model to capture the interdependency of calcium dynamics on glucose uptake and ATP generation...
September 26, 2017: Molecular BioSystems
Alexander V Maltsev, Victor A Maltsev, Michael D Stern
Intracellular Local Ca releases (LCRs) from sarcoplasmic reticulum (SR) regulate cardiac pacemaker cell function by activation of electrogenic Na/Ca exchanger (NCX) during diastole. Prior studies demonstrated the existence of powerful compensatory mechanisms of LCR regulation via a complex local cross-talk of Ca pump, release and NCX. One major obstacle to study these mechanisms is that LCR exhibit complex Ca release propagation patterns (including merges and separations) that have not been characterized. Here we developed new terminology, classification, and computer algorithms for automatic detection of numerically simulated LCRs and examined LCR regulation by SR Ca pumping rate (Pup) that provides a major contribution to fight-or-flight response...
August 2017: PLoS Computational Biology
Ohlrich Marcus, Georg Royl
A hiccup is a reflex movement with diffusely distributed afferents and efferents in the thorax; its functional relevance is controversial. In its physiological form, it is mostly a minor complaint that stops spontaneously and rarely leads to medical consultation. However, prolonged agonizing hiccups represent serious deterioration of quality of life. Chronic hiccups by definition last for more than 48 h, with gastroesophageal reflux being the frequent underlying disease. Various other causes affect multiple organ systems, some with serious underlying diseases...
July 2017: Laryngo- Rhino- Otologie
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