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https://www.readbyqxmd.com/read/29229760/functional-characterization-of-the-ca2-atpase-sma1-from-schistosoma-mansoni
#1
Xavier Maréchal, Ricardo De Mendonça, Roger Miras, Jean Revilloud, Patrice Catty
Schistosoma mansoni is a parasite that causes bilharzia, a neglected tropical disease affecting hundreds of millions of people each year worldwide. In 2012, S. mansoni had been identified as the only invertebrate possessing two SERCA-type Ca2+-ATPases, SMA1 and SMA2. However, our analysis of recent genomic data shows that the presence of two SERCA pumps is rather frequent in parasitic flatworms. To understand the reasons of this redundancy in S. mansoni , we compared SMA1 and SMA2 at different levels. In terms of sequence and organization, the genes SMA1 and SMA2 are similar, suggesting that they might be the result of a duplication event...
December 11, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29222395/extracellular-adenosine-stimulates-vacuolar-atpase-dependent-proton-secretion-in-medullary-intercalated-cells
#2
Maria A Battistone, Anil V Nair, Claire R Barton, Rachel N Liberman, Maria A Peralta, Diane E Capen, Dennis Brown, Sylvie Breton
Acidosis is an important complication of AKI and CKD. Renal intercalated cells (ICs) express the proton pumping vacuolar H+-ATPase (V-ATPase) and are extensively involved in acid-base homeostasis. H+ secretion in type A intercalated cells (A-ICs) is regulated by apical vesicle recycling and stimulated by cAMP. In other cell types, cAMP is increased by extracellular agonists, including adenosine, through purinergic receptors. Adenosine is a Food and Drug Administration-approved drug, but very little is known about the effect of adenosine on IC function...
December 8, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29213101/modulation-of-the-neisseria-gonorrhoeae-drug-efflux-conduit-mtre
#3
Giulia Tamburrino, Salomé Llabrés, Owen N Vickery, Samantha J Pitt, Ulrich Zachariae
Widespread antibiotic resistance, especially of Gram-negative bacteria, has become a severe concern for human health. Tripartite efflux pumps are one of the major contributors to resistance in Gram-negative pathogens, by efficiently expelling a broad spectrum of antibiotics from the organism. In Neisseria gonorrhoeae, one of the first bacteria for which pan-resistance has been reported, the most expressed efflux complex is MtrCDE. Here we present the electrophysiological characterisation of the outer membrane component MtrE and the membrane fusion protein MtrC, obtained by a combination of planar lipid bilayer recordings and in silico techniques...
December 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29211738/metformin-inhibits-the-development-and-promotes-the-resensitization-of-treatment-resistant-breast-cancer
#4
Gerald Davies, Liubov Lobanova, Wojciech Dawicki, Gary Groot, John R Gordon, Matthew Bowen, Troy Harkness, Terra Arnason
Multiple drug resistant (MDR) malignancy remains a predictable and often terminal event in cancer therapy, and affects individuals with many cancer types, regardless of the stage at which they were originally diagnosed or the interval from last treatment. Protein biomarkers of MDR are not globally used for clinical decision-making, but include the overexpression of drug-efflux pumps (ABC transporter family) such as MDR-1 and BCRP, as well as HIF1α, a stress responsive transcription factor found elevated within many MDR tumors...
2017: PloS One
https://www.readbyqxmd.com/read/29210342/antibiotics-potentiating-potential-of-catharanthine-against-superbug-pseudomonas-aeruginosa
#5
Gaurav Raj Dwivedi, Rekha Tyagi, Sanchita Gupta, Shubhandra Tripathi, Sanghamitra Pati, Santosh K Srivastava, Mahendra P Darokar, Ashok Sharma
Multidrug resistance (MDR) put an alarming situation like preantibiotic era which compels us to invigorate the basic science of anti-infective chemotherapy. Hence the drug resistant genes/proteins were explored as promising drug targets. Keeping this thing in mind, proteome of Pseudomonas aeruginosa PA01 was explored, which resulted in the identification of tripartite protein complexes (MexA, MexB and OprM) as promising drug target for the screening of natural and synthetic inhibitors. The purpose of present investigation was to explore the drug resistance reversal potential mechanism of catharanthine isolated from the leaves of Catharanthus roseous...
December 6, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29208689/gestation-changes-sodium-pump-isoform-expression-leading-to-changes-in-ouabain-sensitivity-contractility-and-intracellular-calcium-in-rat-uterus
#6
Rachel V Floyd, Ali Mobasheri, Susan Wray
Developmental and tissue-specific differences in isoforms allow Na+, K+-ATPase function to be tightly regulated, as they control sensitivity to ions and inhibitors. Uterine contraction relies on the activity of the Na+, K+ATPase, which creates ionic gradients that drive excitation-contraction coupling. It is unknown whether Na+, K+ATPase isoforms are regulated throughout pregnancy or whether they have a direct role in modulating uterine contractility. We hypothesized that gestation-dependent differential expression of isoforms would affect contractile responses to Na+, K+ATPase α subunit inhibition with ouabain...
December 2017: Physiological Reports
https://www.readbyqxmd.com/read/29206128/conformational-study-of-z-5-4-chlorobenzylidene-2-4-2-hydroxyethyl-piperazin-1-yl-3h-imidazol-4-5h-one-in-different-environments-insight-into-the-structural-properties-of-bacterial-efflux-pump-inhibitors
#7
Ewa Żesławska, Wojciech Nitek, Jadwiga Handzlik
The 2-amine derivatives of 5-arylidene-3H-imidazol-4(5H)-one are a new class of bacterial efflux pump inhibitors, the chemical compounds that are able to restore antibiotic efficacy against multidrug resistant bacteria. 5-Arylidene-3H-imidazol-4(5H)-ones with a piperazine ring at position 2 reverse the mechanisms of multidrug resistance (MDR) of the particularly dangerous Gram-negative bacteria E. coli by inhibition of the efflux pump AcrA/AcrB/TolC (a main multidrug resistance mechanism in Gram-negative bacteria, consisting of a membrane fusion protein, AcrA, a Resistant-Nodulation-Division protein, AcrB, and an outer membrane factor, TolC)...
December 1, 2017: Acta Crystallographica. Section C, Structural Chemistry
https://www.readbyqxmd.com/read/29177837/high-throughput-flow-cytometry-screening-of-multidrug-efflux-systems
#8
Mark K Haynes, Matthew Garcia, Ryan Peters, Anna Waller, Pietro Tedesco, Oleg Ursu, Cristian G Bologa, Radleigh G Santos, Clemencia Pinilla, Terry H Wu, Julie A Lovchik, Tudor I Oprea, Larry A Sklar, George P Tegos
The resistance nodulation cell division (RND) family of proteins are inner membrane transporters that associate with periplasmic adaptor proteins and outer membrane porins to affect substrate transport from the cytosol and periplasm in Gram-negative bacteria. Various structurally diverse compounds are substrates of RND transporters. Along with their notable role in antibiotic resistance, these transporters are essential for niche colonization, quorum sensing, and virulence as well as for the removal of fatty acids and bile salts...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29161753/improving-the-efficacy-of-proteasome-inhibitors-in-the-treatment-of-renal-cell-carcinoma-by-combination-with-the-hiv-protease-inhibitors-lopinavir-or-nelfinavir
#9
Dominik Abt, Andrej Besse, Lenka Sedlarikova, Marianne Kraus, Juergen Bader, Tobias Silzle, Martina Vodinska, Ondrej Slaby, Hans-Peter Schmid, Daniel Stephan Engeler, Christoph Driessen, Lenka Besse
OBJECTIVES: To assess the potential of second-generation proteasome inhibition by carfilzomib and its combination with the HIV-protease inhibitors (HIV-PIs) lopinavir and nelfinavir in vitro for improved treatment of clear cell renal cell cancer (ccRCC). MATERIALS AND METHODS: Cytotoxicity, reactive oxygen species (ROS) production and unfolded protein response (UPR) activation of proteasome inhibitors, HIV-PIs and their combination was assessed in 3 cell lines and primary cells derived from 3 ccRCC tumors by MTS assay, flow cytometry, quantitative PCR and western blot, respectively...
November 21, 2017: BJU International
https://www.readbyqxmd.com/read/29156525/esomeprazole-ameliorates-ccl4-induced-liver-fibrosis-in-rats-via-modulating-oxidative-stress-inflammatory-fibrogenic-and-apoptotic-markers
#10
Heba M Eltahir, Maiiada H Nazmy
BACKGROUND: Hepatic fibrosis is a major health problem that requires further medical attention. Proton pump inhibitors are proven to possess other therapeutic potentials apart of their acid anti-secretory actions. AIM OF THE WORK: To test possible anti-fibrotic effect of esomeprazole magnesium trihydrate in management of liver fibrosis compared to silymarin, the well-known hepatoprotective agent. MATERIALS & METHODS: 40 male albino rats were divided into 4 groups: normal control group; CCl4-treated group (1 mL/kg 40% CCl4, diluted in olive oil) I...
November 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29145976/not-only-p-glycoprotein-amplification-of-the-abcb1-containing-chromosome-region-7q21-confers-multidrug-resistance-upon-cancer-cells-by-coordinated-overexpression-of-an-assortment-of-resistance-related-proteins
#11
Ilaria Genovese, Andrea Ilari, Yehuda G Assaraf, Francesco Fazi, Gianni Colotti
The development of drug resistance continues to be a dominant hindrance toward curative cancer treatment. Overexpression of a wide-spectrum of ATP-dependent efflux pumps, and in particular of ABCB1 (P-glycoprotein or MDR1) is a well-known resistance mechanism for a plethora of cancer chemotherapeutics including for example taxenes, anthracyclines, Vinca alkaloids, and epipodopyllotoxins, demonstrated by a large array of published papers, both in tumor cell lines and in a variety of tumors, including various solid tumors and hematological malignancies...
May 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/29107658/physiological-characterization-and-regulation-of-the-contractile-properties-of-the-mosquito-ventral-diverticulum-crop
#12
Travis L Calkins, Andrew DeLaat, Peter M Piermarini
In adult dipteran insects (flies), the crop is a diverticulum of the esophagus that serves as a food storage organ. The crop pumps stored contents into the alimentary canal for digestion and absorption. The pumping is mediated by peristaltic contractions of the crop musculature. In adult female mosquitoes, the crop (ventral diverticulum) selectively stores sugar solutions (e.g., nectar); proteinaceous blood meals by-pass the crop and are transferred directly to the midgut for digestion. The mechanisms that regulate crop contractions have never been investigated in mosquitoes...
October 28, 2017: Journal of Insect Physiology
https://www.readbyqxmd.com/read/29107003/elevated-wall-tension-initiates-interleukin-6-expression-and-abdominal-aortic-dilation
#13
Adam W Akerman, Robert E Stroud, Ryan W Barrs, R Tyler Grespin, Lindsay T McDonald, R Amanda C LaRue, Rupak Mukherjee, John S Ikonomidis, Jeffery A Jones, Jean Marie Ruddy
INTRODUCTION: Hypertension (HTN) has long been associated with abdominal aortic aneurysm (AAA) development and these cardiovascular pathologies are biochemically characterized by elevated plasma levels of Angiotensin-II (AngII) as well as interleukin-6 (IL-6). A biologic relationship between HTN and AAA has not been established, however. Accordingly, the objective of this study was to evaluate whether elevated tension may initiate IL-6 production to accumulate monocyte/macrophages and promote dilation of the abdominal aorta (AA)...
October 26, 2017: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/29099466/association-of-proton-pump-inhibitor-use-with-serum-biomarkers-of-inflammation-insulin-resistance-cardiovascular-risk-and-renal-function
#14
Gregory L Austin, Jennifer R Weiskopf, Jennifer L Czwornog
BACKGROUND AND GOALS: Proton pump inhibitor (PPI) use has been associated with cardiovascular disease, chronic kidney disease, and dementia. Prior studies did not account for key confounders and little is known about the association of PPIs with serum biomarkers of inflammation, insulin resistance, cardiovascular risk, and renal function. Our aims were to investigate differences in these biomarkers between PPI users and nonusers. METHODS: Our data are from the National Health and Nutrition Examination Survey (NHANES), a complex cross-sectional multistage probability sample of the US civilian population...
November 3, 2017: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/29098941/efflux-transporter-breast-cancer-resistance-protein-dominantly-expresses-on-the-membrane-of-red-blood-cells-hinders-partitioning-of-its-substrates-into-the-cells-and-alters-drug-drug-interaction-profiles
#15
Pu Shi, Mingxiang Liao, Bei-Ching Chuang, Robert Griffin, Judy Shi, Marc Hyer, John K Fallon, Philip C Smith, Chao Li, Cindy Q Xia
1. Red blood cell (RBC) partitioning is important in determining pharmacokinetic and pharmacodynamic properties of a compound; however, active transport across RBC membranes is not well understood, particularly without transporter-related cell membrane proteomics data. 2. In this study, we quantified breast cancer resistance protein (BCRP/Bcrp) and MDR1/P-glycoprotein (P-gp) protein expression in RBCs from humans, monkeys, dogs, rats, and mice using nanoLC/MS/MS, and evaluated their effect on RBC partitioning and plasma exposure of their substrates...
November 3, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29090346/activation-of-insulin-like-growth-factor-1-receptor-participates-downstream-of-gpr30-in-estradiol-17%C3%AE-d-glucuronide-induced-cholestasis-in-rats
#16
Ismael R Barosso, Gisel S Miszczuk, Nadia Ciriaci, Romina B Andermatten, Paula M Maidagan, Valeria Razori, Diego R Taborda, Marcelo G Roma, Fernando A Crocenzi, Enrique J Sánchez Pozzi
Estradiol-17β-D-glucuronide (E17G), through the activation of different signaling proteins, induces acute endocytic internalization of canalicular transporters in rat, including multidrug resistance-associated protein 2 (Abcc2) and bile salt export pump (Abcb11), generating cholestasis. Insulin-like growth factor 1 receptor (IGF-1R) is a membrane-bound tyrosine kinase receptor that can potentially interact with proteins activated by E17G. The aim of this study was to analyze the potential role of IGF-1R in the effects of E17G in isolated perfused rat liver (IPRL) and isolated rat hepatocyte couplets...
October 31, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29070456/-characterization-of-chromate-resistance-in-genetically-engineered-escherichia-coli-expressing-chromate-ion-transporter-chra
#17
Si-Min Zhou, Lan-Lan Dong, Yuan He, Hong Xiao
OBJECTIVE: To construct a genetically engineered Escherichia coli expressing chromate (Cr) ion transporter ChrA and test its Cr resistance capacity. METHODS: ChrA gene was cloned by PCR from the DNA template of Serratia sp. S2 and linked with the prokaryotic vector pET-28a (+). The recombinant vector was transformed into E.coli BL21 (DE3) cells for expression of ChrA protein. Cr (VI) risistance and Cr (VI) uptake and efflux of the engineered bacteria were tested, and the effects of Cr loading time, oxyanions (ulfate, molybdate, vanadate, tungstate), and respiratory inhibitors (valinomycin, CN(-), oligomycin, and NADH) on Cr (VI) efflux were examined to analyze the pathway of Cr (VI) transport by ChrA protein...
October 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/29069891/additive-effects-of-rebamipide-plus-proton-pump-inhibitors-on-the-expression-of-tight-junction-proteins-in-a-rat-model-of-gastro-esophageal-reflux-disease
#18
Tae-Geun Gweon, Jong-Hyung Park, Byung-Wook Kim, Yang Kyu Choi, Joon Sung Kim, Sung Min Park, Chang Whan Kim, Hyung-Gil Kim, Jun-Won Chung
Background/Aims: The aim of this study was to investigate the effects of rebamipide on tight junction proteins in the esophageal mucosa in a rat model of gastroesophageal reflux disease (GERD). Methods: GERD was created in rats by tying the proximal stomach. The rats were divided into a control group, a proton pump inhibitor (PPI) group, and a PPI plus rebamipide (PPI+R) group. Pantoprazole (5 mg/kg) was administered intraperitoneally to the PPI and PPI+R groups...
October 27, 2017: Gut and Liver
https://www.readbyqxmd.com/read/29032661/a-prospective-study-of-eosinophilic-esophagitis-and-the-expression-of-tight-junction-proteins-in-patients-with-gastroesophageal-reflux-disease-symptoms
#19
Kenichiro Okimoto, Makoto Arai, Hideaki Ishigami, Keiko Saito, Shoko Minemura, Daisuke Maruoka, Tomoaki Matsumura, Tomoo Nakagawa, Tatsuro Katsuno, Masaki Suzuki, Yukio Nakatani, Osamu Yokosuka
Background/Aims: Eosinophilic esophagitis (EoE) is often erroneously diagnosed as gastroesophageal reflex disease (GERD). The aim of this study is to investigate the prevalence of EoE and the expression of tight junction (TJ) proteins in patients with GERD symptoms. Methods: One hundred patients with GERD symptoms and 10 healthy controls were prospectively studied. Sixty-two patients had symptoms refractory to proton pump inhibitors (PPI). All patients underwent esophageal biopsy...
October 17, 2017: Gut and Liver
https://www.readbyqxmd.com/read/29020215/long-term-use-of-proton-pump-inhibitors-is-associated-with-increased-microbial-product-translocation-innate-immune-activation-and-reduced-immunologic-recovery-in-patients-with-chronic-human-immunodeficiency-virus-1-infection
#20
J A Serpa, A M Rueda, A Somasunderam, N S Utay, D Lewis, J P Couturier, K G Breaux, M Rodriguez-Barradas
Background: Translocation of microbial products from the damaged gut causes increased immune activation in human immunodeficiency virus (HIV). Proton pump inhibitors (PPIs) predispose to bacterial overgrowth in the gut. We hypothesized that long-term use of PPIs is associated with greater microbial translocation and immune activation in HIV. Methods: HIV-infected persons on suppressive antiretroviral therapy (ART), including those receiving long-term PPIs (PPI+ group) or not (PPI- group), were enrolled...
October 30, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
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