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Proton pump inhibition

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https://www.readbyqxmd.com/read/29772209/prolyl-hydroxylase-2-a-promising-target-to-inhibit-hypoxia-induced-cellular-metabolism-in-cancer-cells
#1
REVIEW
Lakhveer Singh, Sara Aldosary, Abdulaziz S Saeedan, M Nazam Ansari, Gaurav Kaithwas
Hypoxia-inducible factor-1α (HIF-1α) shifts the metabolism of glucose from highly efficient oxidative phosphorylation to less efficient glycolysis. Pyruvic acid thus accumulated is oxidized to lactic acid which is pumped out in the tumor microenvironment. Protons generated from the pentose phosphate pathway (PPP) and upon hydrolysis of ATP further enhance the acidity in the tumor microenvironment. The resultant pH in the tumor microenvironment activates an endoplasmic reticulum protein: sterol regulatory element binding protein-1c (SREBP-1c), which once activated enhances proliferation of the tumor cell...
May 14, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29754144/mgatp-hydrolysis-destabilizes-the-interaction-between-subunit-h-and-yeast-v1-atpase-highlighting-h-s-role-in-v-atpase-regulation-by-reversible-disassembly
#2
Stuti Sharma, Rebecca A Oot, Stephan Wilkens
Vacuolar H+-ATPases (V-ATPases; V1Vo-ATPases) are rotary motor proton pumps that acidify intracellular compartments and in some tissues, the extracellular space. V-ATPase is regulated by reversible disassembly into autoinhibited V1-ATPase and Vo proton channel sectors. An important player in V-ATPase regulation is subunit H, which binds at the interface of V1 and Vo. H is required for MgATPase activity in holo V-ATPase, but also for stabilizing the MgADP inhibited state in membrane detached V1. However, how H fulfills these two functions is poorly understood...
May 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29739175/potent-potassium-competitive-acid-blockers-a-new-era-for-the-treatment-of-acid-related-diseases
#3
REVIEW
Tadayuki Oshima, Hiroto Miwa
Conventional proton pump inhibitors (PPIs) are used as a first-line therapy to treat acid-related diseases worldwide. However, they have a number of limitations including slow onset of action, influence by cytochrome P450 polymorphisms, unsatisfactory effects at night, and instability in acidic conditions. Alternative formulations of conventional PPIs have been developed to overcome these problems; however, these drugs have only introduced small advantages for controlling acid secretion compared to conventional PPIs...
May 9, 2018: Journal of Neurogastroenterology and Motility
https://www.readbyqxmd.com/read/29738377/proton-pump-inhibition-in-patients-treated-with-novel-antithrombotic-drugs-should-we-worry-about-thrombosis
#4
Tomáš Bolek, Matej Samoš, Ingrid Škorňová, Frantisek Kovář, Peter Galajda, Ján Stasko, Peter Kubisz, Marián Mokáň
Proton pump inhibition (PPI) administrated together with antiplatelet and anticoagulant agents reduces the risk of gastrointestinal hemorrhage. Several novel antithrombotic agents have been recently introduced for acute coronary syndrome patients (prasugrel, ticagrelor), or for patients requiring long-term anticoagulation (dabigatran, rivaroxaban, apixaban, edoxaban, betrixaban). In fact, these agents might offer even stronger inhibition of platelets or coagulation compared with older agents; and therefore, the need for gastroprotection might be even stronger when these new agents are used for long-term antithrombotic therapy...
April 24, 2018: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/29712939/essential-role-of-the-a3-isoform-of-v-atpase-in-secretory-lysosome-trafficking-via-rab7-recruitment
#5
Naomi Matsumoto, Mizuki Sekiya, Koujiro Tohyama, Eri Ishiyama-Matsuura, Ge-Hong Sun-Wada, Yoh Wada, Masamitsu Futai, Mayumi Nakanishi-Matsui
Secretory lysosomes are required for the specialised functions of various types of differentiated cells. In osteoclasts, the lysosomal proton pump V-ATPase (vacuolar-type ATPase) is targeted to the plasma membrane via secretory lysosomes and subsequently acidifies the extracellular compartment, providing optimal conditions for bone resorption. However, little is known about the mechanism underlying this trafficking of secretory lysosomes. Here, we demonstrate that the lysosome-specific a3 isoform of the V-ATPase a subunit plays an indispensable role in secretory lysosome trafficking, together with Rab7, a small GTPase involved in organelle trafficking...
April 30, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29709019/the-seca2-pathway-of-mycobacterium-tuberculosis-exports-effectors-that-work-in-concert-to-arrest-phagosome-and-autophagosome-maturation
#6
Katelyn E Zulauf, Jonathan Tabb Sullivan, Miriam Braunstein
To subvert host defenses, Mycobacterium tuberculosis (Mtb) avoids being delivered to degradative phagolysosomes in macrophages by arresting the normal host process of phagosome maturation. Phagosome maturation arrest by Mtb involves multiple effectors and much remains unknown about this important aspect of Mtb pathogenesis. The SecA2 dependent protein export system is required for phagosome maturation arrest and consequently growth of Mtb in macrophages. To better understand the role of the SecA2 pathway in phagosome maturation arrest, we identified two effectors exported by SecA2 that contribute to this process: the phosphatase SapM and the kinase PknG...
April 30, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29665355/combination-therapy-with-polydeoxyribonucleotide-and-proton-pump-inhibitor-enhances-therapeutic-effectiveness-for-gastric-ulcer-in-rats
#7
Il-Gyu Ko, Sung-Eun Kim, Jun-Jang Jin, Lakkyong Hwang, Eun-Sang Ji, Chang-Ju Kim, Jin-Hee Han, In Taik Hong, Min Seop Kwak, Jin Young Yoon, Hyun Phil Shin, Jung Won Jeon
AIMS: The main action of proton pump inhibitors (PPIs) is to inhibit gastric acid secretion, and PPIs are widely used to treat gastric ulcer (GU). However, if the action of promoting gastric mucosal regeneration is added, the effectiveness of GU treatment can be enhanced. Thus, in order to improve the therapeutic effect on GU, we tried to develop combination therapy promoting regeneration in injured tissue besides suppressing gastric acid secretion. MAIN METHODS: Polydeoxyribonucleotide (PDRN) was selected to evaluate tissue regeneration, and pantoprazole was chosen as one of the PPIs...
April 14, 2018: Life Sciences
https://www.readbyqxmd.com/read/29656158/toxicogenetic-study-of-omeprazole-and-the-modulatory-effects-of-retinol-palmitate-and-ascorbic-acid-on-allium-cepa
#8
Antonio Lima Braga, Ag-Anne Pereira Melo de Meneses, José Victor de Oliveira Santos, Antonielly Campinho Dos Reis, Rosália Maria Tôrres de Lima, Ana Maria Oliveira Ferreira da Mata, Márcia Fernanda Correia Jardim Paz, Leane Brunelle Dos Santos Alves, Subrata Shaw, Shaikh Jamal Uddin, Razina Rouf, Asish Kumar Das, Shrabanti Dev, Manik Chandra Shil, Jamil A Shilpi, Ishaq N Khan, Muhammad Torequl Islam, Eunüs S Ali, Mohammad S Mubarak, Siddhartha Kumar Mishra, João Marcelo de Castro E Sousa, Ana Amélia de Carvalho Melo-Cavalcante
Omeprazole (OME) is a proton pump inhibitor used for the treatment of various gastric and intestinal disease; however, studies on its effects on the genetic materials are still restricted. The present study aimed to evaluate possible toxicogenic effects of OME in Allium cepa meristems with the application of cytogenetic biomarkers for DNA damage, mutagenic, toxic and cytotoxic effects. Additionally, retinol palmitate (RP) and ascorbic acid (AA) were also co-treated with OME to evaluate possible modulatory effects of OME-induced cytogenetic damages...
April 5, 2018: Chemosphere
https://www.readbyqxmd.com/read/29605975/advantages-and-disadvantages-of-long-term-proton-pump-inhibitor-use
#9
REVIEW
Yoshikazu Kinoshita, Norihisa Ishimura, Shunji Ishihara
Proton pump inhibitors (PPIs) potently inhibit gastric acid secretion and are widely used for treatment of acid-related diseases including gastroesophageal reflux disease and secondary prevention of aspirin/NSAID-induced ulcers. Although clinically important adverse effects of PPIs can occur, just as with other drugs, those are not frequently observed during or after administration. Thus, PPIs are regarded as relatively safe and considered to be clinically beneficial. Recently, PPIs have become frequently administered to patients with functional gastrointestinal diseases or primary prevention of drug-related gastroduodenal damage, even though their beneficial effects for those conditions have not been fully confirmed...
April 30, 2018: Journal of Neurogastroenterology and Motility
https://www.readbyqxmd.com/read/29600697/pharmacological-considerations-and-step-by-step-proposal-for-the-treatment-of-helicobacter-pylori-infection-in-the-year-2018
#10
Rinaldo Pellicano, Rocco M Zagari, Songhua Zhang, Giorgio M Saracco, Steven F Moss
Over the past 30 years, multidrug regimens consisting of a proton pump inhibitor (PPI) and two or three antibiotics have been used in treating Helicobacter pylori (H. pylori) infection. In clinical practice, the optimal regimen to cure H. pylori infection should be decided regionally. Considering the first treatment, the Maastricht V/Florence Consensus Report and the American College of Gastroenterology Clinical Management Guideline highlight that in countries with low clarithromycin resistance rates (<15%), an empiric clarithromycin-based regimen can be used...
March 30, 2018: Minerva Gastroenterologica e Dietologica
https://www.readbyqxmd.com/read/29567836/histone-deacetylase-mediated-regulation-of-endolysosomal-ph
#11
Hari Prasad, Rajini Rao
The pH of the endolysosomal system is tightly regulated by a balance of proton pump and leak mechanisms that are critical for storage, recycling, turnover, and signaling functions in the cell. Dysregulation of endolysosomal pH has been linked to aging, amyloidogenesis, synaptic dysfunction, and various neurodegenerative disorders, including Alzheimer's disease. Therefore, understanding the mechanisms that regulate luminal pH may be key to identifying new targets for managing these disorders. Metaanalysis of yeast microarray databases revealed that nutrient limiting conditions inhibited the histone deacetylase (HDAC) Rpd3 and thereby upregulated transcription of the endosomal Na+ /H+ exchanger Nhx1, resulting in vacuolar alkalinization...
March 22, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29563046/bcpp-compounds-pet-probes-for-early-therapeutic-evaluations-specifically-bind-to-mitochondrial-complex-i
#12
Sayaka Kazami, Shingo Nishiyama, Yuji Kimura, Hiroyasu Itoh, Hideo Tsukada
BCPP compounds have been developed as PET imaging probes for neurodegenerative diseases in the living brain.18 F-BCPP-EF identifies damaged neuronal areas based on the lack of MC-I; however, its underlying mechanisms of action and specificity for MC-I remain unclear. We herein report the effects of BCPP-BF, -EF, -EM on MC-I in respiratory chain complexes using cardiomyocyte SMP. BCPP compounds inhibited the binding of3 H-dihydrorotenone to MC-I and the proton pumping activity of MC-I in a concentration-dependent manner in vitro...
March 18, 2018: Mitochondrion
https://www.readbyqxmd.com/read/29562219/preferential-ty1-retromobility-in-mother-cells-and-nonquiescent-stationary-phase-cells-is-associated-with-increased-concentrations-of-total-gag-or-processed-gag-and-is-inhibited-by-exposure-to-a-high-concentration-of-calcium
#13
Andrew C Peifer, Patrick H Maxwell
Retrotransposons are abundant mobile DNA elements in eukaryotic genomes that are more active with age in diverse species. Details of the regulation and consequences of retrotransposon activity during aging remain to be determined. Ty1 retromobility in Saccharomyces cerevisiae is more frequent in mother cells compared to daughter cells, and we found that Ty1 was more mobile in nonquiescent compared to quiescent subpopulations of stationary phase cells. This retromobility asymmetry was absent in mutant strains lacking BRP1 that have reduced expression of the essential Pma1p plasma membrane proton pump, lacking the mRNA decay gene LSM1 , and in cells exposed to a high concentration of calcium...
March 21, 2018: Aging
https://www.readbyqxmd.com/read/29530525/porphyromonas-gingivalis-is-highly-sensitive-to-inhibitors-of-a-proton-pumping-atpase
#14
Mizuki Sekiya, Yu Shimoyama, Taichi Ishikawa, Minoru Sasaki, Masamitsu Futai, Mayumi Nakanishi-Matsui
Porphyromonas gingivalis is a well-known Gram-negative bacterium that causes periodontal disease. The bacterium metabolizes amino acids and peptides to obtain energy. An ion gradient across its plasma membrane is thought to be essential for nutrient import. However, it is unclear whether an ion-pumping ATPase responsible for the gradient is required for bacterial growth. Here, we report the inhibitory effect of protonophores and inhibitors of a proton-pumping ATPase on the growth of P. gingivalis. Among the compounds examined, curcumin and citreoviridin appreciably reduced the bacterial growth...
April 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29522317/2-mercapto-quinazolinones-as-inhibitors-of-type-ii-nadh-dehydrogenase-and-mycobacterium-tuberculosis-structure-activity-relationships-mechanism-of-action-and-absorption-distribution-metabolism-and-excretion-characterization
#15
Dinakaran Murugesan, Peter C Ray, Tracy Bayliss, Gareth A Prosser, Justin R Harrison, Kirsteen Green, Candice Soares de Melo, Tzu-Shean Feng, Leslie J Street, Kelly Chibale, Digby F Warner, Valerie Mizrahi, Ola Epemolu, Paul Scullion, Lucy Ellis, Jennifer Riley, Yoko Shishikura, Liam Ferguson, Maria Osuna-Cabello, Kevin D Read, Simon R Green, Dirk A Lamprecht, Peter M Finin, Adrie J C Steyn, Thomas R Ioerger, Jim Sacchettini, Kyu Y Rhee, Kriti Arora, Clifton E Barry, Paul G Wyatt, Helena I M Boshoff
Mycobacterium tuberculosis ( MTb) possesses two nonproton pumping type II NADH dehydrogenase (NDH-2) enzymes which are predicted to be jointly essential for respiratory metabolism. Furthermore, the structure of a closely related bacterial NDH-2 has been reported recently, allowing for the structure-based design of small-molecule inhibitors. Herein, we disclose MTb whole-cell structure-activity relationships (SARs) for a series of 2-mercapto-quinazolinones which target the ndh encoded NDH-2 with nanomolar potencies...
March 26, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29485009/oral-submucous-fibrosis-as-an-overhealing-wound-implications-in-malignant-transformation
#16
Mohit Sharma, Smitha Sammith Shetty, Raghu Radhakrishnan
BACKGROUND: Oral submucous fibrosis is an oral potentially malignant disorder with high incidence of malignant transformation and rising global prevalence. However, the genesis of oral submucous fibrosis is still unclear despite superfluity of literature. In the background of ineffective treatment, it is necessary to decode its onset and progression before designing customized treatment regimens. OBJECTIVE: The objective of this article is to decipher the pathogenesis of oral submucous fibrosis in order to identify novel drug targets...
February 26, 2018: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/29477057/maintenance-proton-pump-inhibition-therapy-and-risk-of-oesophageal-cancer
#17
Nele Brusselaers, Lars Engstrand, Jesper Lagergren
BACKGROUND: The association of long-term use of proton pump inhibitors (PPIs) with oesophageal adenocarcinoma has been poorly defined. Our aim was to assess the risk of oesophageal cancer assessing confounding by indication. METHODS: This population-based cohort study included all 796,492 adults exposed to maintenance therapy with PPIs in Sweden in 2005-2012. Standardised incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated to assess the risk of oesophageal adenocarcinoma (and squamous cell carcinoma as a comparison) among long-term PPI users relative to the corresponding background population...
April 2018: Cancer Epidemiology
https://www.readbyqxmd.com/read/29464421/two-inhibitors-of-yeast-plasma-membrane-atpase-1-scpma1p-toward-the-development-of-novel-antifungal-therapies
#18
Sabine Ottilie, Gregory M Goldgof, Andrea L Cheung, Jennifer L Walker, Edgar Vigil, Kenneth E Allen, Yevgeniya Antonova-Koch, Carolyn W Slayman, Yo Suzuki, Jacob D Durrant
Given that many antifungal medications are susceptible to evolved resistance, there is a need for novel drugs with unique mechanisms of action. Inhibiting the essential proton pump Pma1p, a P-type ATPase, is a potentially effective therapeutic approach that is orthogonal to existing treatments. We identify NSC11668 and hitachimycin as structurally distinct antifungals that inhibit yeast ScPma1p. These compounds provide new opportunities for drug discovery aimed at this important target.
February 20, 2018: Journal of Cheminformatics
https://www.readbyqxmd.com/read/29453559/regulation-of-h-pyrophosphatase-by-14-3-3-proteins-from-arabidopsis-thaliana
#19
Yu-Di Hsu, Yu-Fen Huang, Yih-Jiuan Pan, Li-Kun Huang, Ya-Yun Liao, Wei-Hua Lin, Tzu-Yin Liu, Ching-Hung Lee, Rong-Long Pan
Plant vacuolar H+ -transporting inorganic pyrophosphatase (V-PPase; EC 3.6.1.1) is a crucial enzyme that exists on the tonoplast to maintain pH homeostasis across the vacuolar membrane. This enzyme generates proton gradient between cytosol and vacuolar lumen by hydrolysis of a metabolic byproduct, pyrophosphate (PP i ). The regulation of V-PPase at protein level has drawn attentions of many workers for decades, but its mechanism is still unclear. In this work, we show that AVP1, the V-PPase from Arabidopsis thaliana, is a target protein for regulatory 14-3-3 proteins at the vacuolar membrane, and all twelve 14-3-3 isoforms were analyzed for their association with AVP1...
April 2018: Journal of Membrane Biology
https://www.readbyqxmd.com/read/29449127/evaluating-the-effect-of-six-proton-pump-inhibitors-on-the-antiplatelet-effects-of-clopidogrel
#20
Eugene R Przespolewski, Erica S Westphal, Michelle Rainka, Nicholas M Smith, Vernice Bates, Fran M Gengo
BACKGROUND AND GOAL: Cytochrome P450 (CYP) enzymes are responsible for the conversion of clopidogrel into its active metabolite and the metabolism of proton pump inhibitors (PPIs), which may also inhibit CYP enzymes. A current Food and Drug Administration advisory suggests avoiding esomeprazole and omeprazole while taking clopidogrel because of concerns that PPIs may compromise clopidogrel's antiplatelet effects. The objective of the present study was to examine the robustness of this interaction using a well-controlled study design in a population of participants free of confounders...
June 2018: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
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