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pH homeostasis

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https://www.readbyqxmd.com/read/29047094/endothelial-cell-reactive-oxygen-species-and-ca-2-signaling-in-pulmonary-hypertension
#1
Karthik Suresh, Larissa A Shimoda
Pulmonary hypertension (PH) refers to a disorder characterized by elevated pulmonary arterial pressure, leading to right ventricular overload and eventually right ventricular failure, which results in high morbidity and mortality. PH is associated with heterogeneous etiologies and distinct molecular mechanisms, including abnormal migration and proliferation of endothelial and smooth muscle cells. Although the exact details are not fully elucidated, reactive oxygen species (ROS) have been shown to play a key role in promoting abnormal function in pulmonary arterial smooth muscle and endothelial cells in PH...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29047083/altered-redox-balance-in-the-development-of-chronic-hypoxia-induced-pulmonary-hypertension
#2
Nikki L Jernigan, Thomas C Resta, Laura V Gonzalez Bosc
Normally, the pulmonary circulation is maintained in a low-pressure, low-resistance state with little resting tone. Pulmonary arteries are thin-walled and rely heavily on pulmonary arterial distension and recruitment for reducing pulmonary vascular resistance when cardiac output is elevated. Under pathophysiological conditions, however, active vasoconstriction and vascular remodeling lead to enhanced pulmonary vascular resistance and subsequent pulmonary hypertension (PH). Chronic hypoxia is a critical pathological factor associated with the development of PH resulting from airway obstruction (COPD, sleep apnea), diffusion impairment (interstitial lung disease), developmental lung abnormalities, or high altitude exposure (World Health Organization [WHO]; Group III)...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29047079/molecular-basis-of-nitrative-stress-in-the-pathogenesis-of-pulmonary-hypertension
#3
Colin E Evans, You-Yang Zhao
Pulmonary hypertension (PH) is a lung vascular disease with marked increases in pulmonary vascular resistance and pulmonary artery pressure (>25 mmHg at rest). In PH patients, increases in pulmonary vascular resistance lead to impaired cardiac output and reduced exercise tolerance. If untreated, PH progresses to right heart failure and premature lethality. The mechanisms that control the pathogenesis of PH are incompletely understood, but evidence from human and animal studies implicate nitrative stress in the development of PH...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29038303/f-actin-reorganization-by-v-atpase-inhibition-in-prostate-cancer
#4
Yamhilette Licon-Munoz, Vera Michel, Colleen A Fordyce, Karlett J Parra
The vacuolar ATPase (V-ATPase) proton pump sustains cellular pH homeostasis, and its inhibition triggers numerous stress responses. However, the cellular mechanisms involved remain largely elusive in cancer cells. We studied V-ATPase in the prostate cancer (PCa) cell line PC-3, which has characteristics of highly metastatic PCa. V-ATPase inhibitors impaired endo-lysosomal pH, vesicle trafficking, migration, and invasion. V-ATPase accrual in the Golgi and recycling endosomes suggests that traffic of internalized membrane vesicles back to the plasma membrane was particularly impaired...
October 16, 2017: Biology Open
https://www.readbyqxmd.com/read/29033900/weak-organic-acids-decrease-borrelia-burgdorferi-cytoplasmic-ph-eliciting-an-acid-stress-response-and-impacting-rpon-and-rpos-dependent-gene-expression
#5
Daniel P Dulebohn, Crystal L Richards, Hua Su, Kevin A Lawrence, Frank C Gherardini
The spirochete Borrelia burgdorferi survives in its tick vector, Ixodes scapularis, or within various hosts. To transition between and survive in these distinct niches, B. burgdorferi changes its gene expression in response to environmental cues, both biochemical and physiological. Exposure of B. burgdorferi to weak monocarboxylic organic acids, including those detected in the blood meal of fed ticks, decreased the cytoplasmic pH of B. burgdorferi in vitro. A decrease in the cytoplasmic pH induced the expression of genes encoding enzymes that have been shown to restore pH homeostasis in other bacteria...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29026134/mct1-and-mct4-expression-and-lactate-flux-activity-increase-during-white-and-brown-adipogenesis-and-impact-adipocyte-metabolism
#6
Charlotte Petersen, Mette D Nielsen, Elise S Andersen, Astrid L Basse, Marie S Isidor, Lasse K Markussen, Birgitte M Viuff, Ian H Lambert, Jacob B Hansen, Stine F Pedersen
Adipose tissue takes up glucose and releases lactate, thereby contributing significantly to systemic glucose and lactate homeostasis. This implies the necessity of upregulation of net acid and lactate flux capacity during adipocyte differentiation and function. However, the regulation of lactate- and acid/base transporters in adipocytes is poorly understood. Here, we tested the hypothesis that adipocyte thermogenesis, browning and differentiation are associated with an upregulation of plasma membrane lactate and acid/base transport capacity that in turn is important for adipocyte metabolism...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29019983/human-trpml1-channel-structures-in-open-and-closed-conformations
#7
Philip Schmiege, Michael Fine, Günter Blobel, Xiaochun Li
Transient receptor potential mucolipin 1 (TRPML1) is a Ca(2+)-releasing cation channel that mediates the calcium signalling and homeostasis of lysosomes. Mutations in TRPML1 lead to mucolipidosis type IV, a severe lysosomal storage disorder. Here we report two electron cryo-microscopy structures of full-length human TRPML1: a 3.72-Å apo structure at pH 7.0 in the closed state, and a 3.49-Å agonist-bound structure at pH 6.0 in an open state. Several aromatic and hydrophobic residues in pore helix 1, helices S5 and S6, and helix S6 of a neighbouring subunit, form a hydrophobic cavity to house the agonist, suggesting a distinct agonist-binding site from that found in TRPV1, a TRP channel from a different subfamily...
October 11, 2017: Nature
https://www.readbyqxmd.com/read/29018191/d-serine-released-by-astrocytes-in-brainstem-regulates-breathing-response-to-co2-levels
#8
S Beltrán-Castillo, M J Olivares, R A Contreras, G Zúñiga, I Llona, R von Bernhardi, J L Eugenín
Central chemoreception is essential for adjusting breathing to physiological demands, and for maintaining CO2 and pH homeostasis in the brain. CO2-induced ATP release from brainstem astrocytes stimulates breathing. NMDA receptor (NMDAR) antagonism reduces the CO2-induced hyperventilation by unknown mechanisms. Here we show that astrocytes in the mouse caudal medullary brainstem can synthesize, store, and release D-serine, an agonist for the glycine-binding site of the NMDAR, in response to elevated CO2 levels...
October 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28994701/study-of-statin-and-loratadine-induced-muscle-pain-mechanisms-using-human-skeletal-muscle-cells
#9
Yat Hei Leung, Jacques Turgeon, Veronique Michaud
Many drugs can cause unexpected muscle disorders, often necessitating the cessation of an effective medication. Inhibition of monocarboxylate transporters (MCTs) may potentially lead to perturbation of l-lactic acid homeostasis and muscular toxicity. Previous studies have shown that statins and loratadine have the potential to inhibit l-lactic acid efflux by MCTs (MCT1 and 4). The main objective of this study was to confirm the inhibitory potentials of atorvastatin, simvastatin (acid and lactone forms), rosuvastatin, and loratadine on l-lactic acid transport using primary human skeletal muscle cells (SkMC)...
October 10, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/28994450/the-role-of-transient-receptor-potential-channels-in-joint-diseases
#10
O Krupkova, J Zvick, K Wuertz-Kozak
Transient receptor potential channels (TRP channels) are cation selective transmembrane receptors with diverse structures, activation mechanisms and physiological functions. TRP channels act as cellular sensors for a plethora of stimuli, including temperature, membrane voltage, oxidative stress, mechanical stimuli, pH and endogenous, as well as, exogenous ligands, thereby illustrating their versatility. As such, TRP channels regulate various functions in both excitable and non-excitable cells, mainly by mediating Ca2+ homeostasis...
October 10, 2017: European Cells & Materials
https://www.readbyqxmd.com/read/28978047/restoring-microenvironmental-redox-and-ph-homeostasis-inhibits-neoplastic-cell-growth-and-migration-therapeutic-efficacy-of-esomeprazole-plus-sulfasalazine-on-3-mca-induced-sarcoma
#11
Enrica Balza, Patrizia Castellani, Paola Sanchez Moreno, Patrizia Piccioli, Iria Medraño-Fernandez, Claudia Semino, Anna Rubartelli
Neoplastic cells live in a stressful context and survive thanks to their ability to overcome stress. Thus, tumor cell responses to stress are potential therapeutic targets. We selected two such responses in melanoma and sarcoma cells: the xc- antioxidant system, that opposes oxidative stress, and surface v-ATPases that counteract the low pHi by extruding protons, and targeted them with the xc- blocker sulfasalazine and the proton pump inhibitor esomeprazole. Sulfasalazine inhibited the cystine/cysteine redox cycle and esomeprazole decreased pHi while increasing pHe in tumor cell lines...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28975383/intrinsic-thermodynamics-of-high-affinity-inhibitor-binding-to-recombinant-human-carbonic-anhydrase-iv
#12
Aurelija Mickevičiūtė, David D Timm, Marius Gedgaudas, Vaida Linkuvienė, Zhiwei Chen, Abdul Waheed, Vilma Michailovienė, Asta Zubrienė, Alexey Smirnov, Edita Čapkauskaitė, Lina Baranauskienė, Jelena Jachno, Jurgita Revuckienė, Elena Manakova, Saulius Gražulis, Jurgita Matulienė, Enrico Di Cera, William S Sly, Daumantas Matulis
Membrane-associated carbonic anhydrase (CA) isoform IV participates in carbon metabolism and pH homeostasis and is implicated in the development of eye diseases such as retinitis pigmentosa and glaucoma. A series of substituted benzenesulfonamides were designed and their binding affinity to CA IV was determined by fluorescent thermal shift assay and isothermal titration calorimetry (ITC). Compound [(4-chloro-2-phenylsulfanyl-5-sulfamoyl-benzoyl)amino]propyl acetate (19) bound CA IV with the K d of 1.0 nM and exhibited significant selectivity over the remaining 11 human CA isoforms...
October 3, 2017: European Biophysics Journal: EBJ
https://www.readbyqxmd.com/read/28972616/design-and-validation-of-a-new-ratiometric-intracellular-ph-imaging-probe-using-lanthanide-doped-upconverting-nanoparticles
#13
Shuoren Du, Javier Hernández-Gil, Hao Dong, Xiaoyu Zheng, Guangming Lyu, Manuel Bañobre-López, Juan Gallo, Ling-Dong Sun, Chun-Hua Yan, Nicholas J Long
pH homeostasis is strictly controlled at a subcellular level. A deregulation of the intra/extra/subcellular pH environment is associated with a number of diseases and as such, the monitoring of the pH state of cells and tissues is a valuable diagnostic tool. To date, only a few tools have been developed to measure the pH in living cells with the spatial resolution needed for intracellular imaging. Among the techniques available, only optical imaging offers enough resolution and biocompatibility to be proposed for subcellular pH monitoring...
October 17, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28965917/phospholipid-composition-of-packed-red-blood-cells-and-that-of-extracellular-vesicles-show-a-high-resemblance-and-stability-during-storage
#14
Eva Laurén, Feven Tigistu-Sahle, Sami Valkonen, Melissa Westberg, Anne Valkeajärvi, Juha Eronen, Pia Siljander, Ville Pettilä, Reijo Käkelä, Saara Laitinen, Erja Kerkelä
Red blood cells (RBCs) are stored up to 35-42days at 2-6°C in blood banks. During storage, the RBC membrane is challenged by energy depletion, decreasing pH, altered cation homeostasis, and oxidative stress, leading to several biochemical and morphological changes in RBCs and to shedding of extracellular vesicles (EVs) into the storage medium. These changes are collectively known as RBC storage lesions. EVs accumulate in stored RBC concentrates and are, thus, transfused into patients. The potency of EVs as bioactive effectors is largely acknowledged, and EVs in RBC concentrates are suspected to mediate some adverse effects of transfusion...
September 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28944093/ypt4-and-lvs1-regulate-vacuolar-size-and-function-in-schizosaccharomyces-pombe
#15
Addison Rains, Yorisha Bryant, Kaitlyn A Dorsett, Austin Culver, Jamal Egbaria, Austin Williams, Matt Barnes, Raeann Lamere, Austin R Rossi, Stephanie C Waldrep, Caroline Wilder, Elliot Kliossis, Melanie L Styers
The yeast vacuole plays key roles in cellular stress responses. Here, we show that deletion of lvs1, the fission yeast homolog of the Chediak-Higashi Syndrome CHS1/LYST gene, increases vacuolar size, similar to deletion of the Rab4 homolog ypt4. Overexpression of lvs1-YFP rescued vacuolar size in ypt4Δ cells, but ypt4-YFP did not rescue lvs1Δ, suggesting that lvs1 may act downstream of ypt4. Vacuoles were capable of hypotonic shock-induced fusion and recovery in both ypt4Δ and lvs1Δ cells, although recovery may be slightly delayed in ypt4Δ...
2017: Cellular Logistics
https://www.readbyqxmd.com/read/28944006/regulation-of-gene-expression-is-associated-with-tolerance-of-the-arctic-copepod-calanus-glacialis-to-co2-acidified-sea-water
#16
Allison Bailey, Pierre De Wit, Peter Thor, Howard I Browman, Reidun Bjelland, Steven Shema, David M Fields, Jeffrey A Runge, Cameron Thompson, Haakon Hop
Ocean acidification is the increase in seawater pCO 2 due to the uptake of atmospheric anthropogenic CO 2, with the largest changes predicted to occur in the Arctic seas. For some marine organisms, this change in pCO 2, and associated decrease in pH, represents a climate change-related stressor. In this study, we investigated the gene expression patterns of nauplii of the Arctic copepod Calanus glacialis cultured at low pH levels. We have previously shown that organismal-level performance (development, growth, respiration) of C...
September 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28941238/discovery-of-antimicrobial-peptides-in-cervical-vaginal-fluid-from-healthy-non-pregnant-women-via-an-integrated-proteome-and-peptidome-analysis
#17
Carla M J Muytjens, Yijing Yu, Eleftherios P Diamandis
Cervical-vaginal fluid (CVF) covers the lower part of the female reproductive system and functions in the homeostasis and immunity of the surrounding tissues. In contrast to the CVF proteome of both non-pregnant and pregnant women, the CVF peptidome has not been reported to date. In the current study, we identified 1,087 proteins in CVF, of which 801 proteins were not previously identified in CVF proteomes. The presence of the tissue-specific proteins oviductal glycoprotein-1 (OVGP-1) and tubulin polymerization-promoting protein family member 3 (TPPP3) strongly suggests that the tissues of the upper female reproductive tract contribute to the protein composition of CVF...
September 23, 2017: Proteomics
https://www.readbyqxmd.com/read/28935723/draft-genome-sequence-of-natronolimnobius-baerhuensis-cgmcc-1-3597-t-an-aerobic-haloalkaliphilic-archaeon-isolated-from-a-soda-lake
#18
Xiaomeng Guo, Ziya Liao, Yanchun Yan, Mark Holtzapple, Qingping Hu, Baisuo Zhao
The haloalkaliphilic archaeon Natronolimnobius baerhuensis was isolated from a soda lake in Inner Mongolia (China), growing optimally at about 20% NaCl and pH 9.0. The draft genome consists of approximately 3.91 Mb and contains 3,810 predicted genes. Some genes that regulate intracellular osmotic stress and pH homeostasis were identified, providing insight into specific adaptations to this double-extreme environment.
September 21, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28930993/confocal-imaging-of-neuropeptide-y-phluorin-a-technique-to-visualize-insulin-granule-exocytosis-in-intact-murine-and-human-islets
#19
Madina Makhmutova, Tao Liang, Herbert Gaisano, Alejandro Caicedo, Joana Almaça
Insulin secretion plays a central role in glucose homeostasis under normal physiological conditions as well as in disease. Current approaches to study insulin granule exocytosis either use electrophysiology or microscopy coupled to the expression of fluorescent reporters. However most of these techniques have been optimized for clonal cell lines or require dissociating pancreatic islets. In contrast, the method presented here allows for real time visualization of insulin granule exocytosis in intact pancreatic islets...
September 13, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28922497/mutual-independence-of-alkaline-and-calcium-mediated-signalling-in-aspergillus-fumigatus-refutes-the-existence-of-a-conserved-druggable-signalling-nexus
#20
Omar Loss, Margherita Bertuzzi, Yu Yan, Natalie Fedorova, Bethany L McCann, Darius Armstrong-James, Eduardo A Espeso, Nick D Read, William C Nierman, Elaine M Bignell
Functional coupling of calcium- and alkaline responsive signalling occurs in multiple fungi to afford efficient cation homeostasis. Host microenvironments exert alkaline stress and potentially toxic concentrations of Ca(2+) , such that highly conserved regulators of both calcium- (Crz) and pH- (PacC/Rim) responsive signalling are crucial for fungal pathogenicity. Drugs targeting calcineurin are potent antifungal agents but also perturb human immunity thereby negating their use as anti-infectives, abrogation of alkaline signalling has therefore been postulated as an adjunctive antifungal strategy...
September 18, 2017: Molecular Microbiology
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