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Intracellular acidosis

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https://www.readbyqxmd.com/read/29132215/in-vivo-molecular-epr-based-spectroscopy-and-imaging-of-tumor-microenvironment-and-redox-using-functional-paramagnetic-probes
#1
Valery V Khramtsov
<i><b>Significance:</b></i> A key role of the tumor microenvironment (TME) in cancer progression, treatment resistance and as a target for therapeutic intervention is increasingly appreciated. Among physiological components of the TME are tissue hypoxia, acidosis, high reducing capacity, elevated concentrations of intracellular glutathione (GSH) and interstitial inorganic phosphate (Pi). Noninvasive <i>in vivo</i> assessment of these parameters provide unique insights into biological processes in TME, and may serve as a tool for pre-clinical screening of anticancer drugs and optimizing TME-targeted therapeutic strategies...
November 13, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29101173/ph-recovery-from-a-proton-load-in-rat-cardiomyocytes-effects-of-chronic-exercise
#2
Vennetia R Danes, Josephine Anthony, Kaveh Rayani, Kenneth W Spitzer, Glen F Tibbits
The ability of cardiomyocytes to recover from a proton load was examined in the hearts of exercise-trained (T) and sedentary control (C) rats in CO2/HCO3--free media. Acidosis was created by the NH4Cl pre-pulse technique and pHi was determined using fluorescence microscopy on carboxy-SNARF-1 AM loaded isolated cardiomyocytes. CO2-independent intracellular pH buffering capacity (βi) was measured by incrementally reducing the [NH4Cl]o in steps of 50% from 20 to 1.25 mM. βi increased as pHi decreased in both T and C groups...
November 3, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29093223/identification-of-a-molecular-ph-sensor-in-coral
#3
Katie L Barott, Megan E Barron, Martin Tresguerres
Maintaining stable intracellular pH (pHi) is essential for homeostasis, and requires the ability to both sense pH changes that may result from internal and external sources, and to regulate downstream compensatory pH pathways. Here we identified the cAMP-producing enzyme soluble adenylyl cyclase (sAC) as the first molecular pH sensor in corals. sAC protein was detected throughout coral tissues, including those involved in symbiosis and calcification. Application of a sAC-specific inhibitor caused significant and reversible pHi acidosis in isolated coral cells under both dark and light conditions, indicating sAC is essential for sensing and regulating pHi perturbations caused by respiration and photosynthesis...
November 15, 2017: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/29032102/regulation-of-ca-2-signaling-by-acute-hypoxia-and-acidosis-in-rat-neonatal-cardiomyocytes
#4
José-Carlos Fernández-Morales, Martin Morad
Ischemic heart disease is an arrhythmogenic condition, accompanied by hypoxia, acidosis, and impaired Ca(2+) signaling. Here we report on effects of acute hypoxia and acidification in rat neonatal cardiomyocytes cultures. RESULTS: Two populations of neonatal cardiomyocyte were identified based on inactivation kinetics of L-type ICa: rapidly-inactivating ICa (τ~20ms) myocytes (prevalent in 3-4-day cultures), and slow-inactivating ICa (τ≥40ms) myocytes (dominant in 7-day cultures). Acute hypoxia (pO2<5mmHg for 50-100s) suppressed ICa reversibly in both cell-types to different extent and with different kinetics...
October 12, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28986307/interleukin-1%C3%AE-and-tumor-necrosis-factor-%C3%AE-augment-acidosis-induced-rat-articular-chondrocyte-apoptosis-via-nuclear-factor-kappab-dependent-upregulation-of-asic1a-channel
#5
Ren-Peng Zhou, Bei-Bei Dai, Ya-Ya Xie, Xiao-Shan Wu, Zhi-Sen Wang, Yue Li, Zhi-Qiang Wang, Sheng-Qin Zu, Jin-Fang Ge, Fei-Hu Chen
The acute-phase proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) demonstrate high-level expression and pleiotropic biological effects, and contribute to the progression and persistence of rheumatoid arthritis (RA). Acid hydrarthrosis is also an important pathological characteristic of RA, and the acid-sensing ion channel 1a (ASIC1a) plays a critical role in acidosis-induced chondrocyte cytotoxicity. However, the roles of IL-1β and TNF-α in acid-induced apoptosis of chondrocytes remain unclear...
October 3, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28984162/acid-base-regulation-and-sensing-accelerators-and-brakes-in-metabolic-regulation-of-cerebrovascular-tone
#6
Ebbe Boedtkjer
Metabolic regulation of cerebrovascular tone directs blood flow to areas of increased neuronal activity and during disease states partially compensates for insufficient perfusion by enhancing blood flow in collateral blood vessels. Acid-base disturbances frequently occur as result of enhanced metabolism or insufficient blood supply, but despite definitive evidence that acid-base disturbances alter arterial tone, effects of individual acid-base equivalents and the underlying signaling mechanisms are still being debated...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28978009/tumor-antigen-glycosaminoglycan-modification-regulates-antibody-drug-conjugate-delivery-and-cytotoxicity
#7
Helena C Christianson, Julien A Menard, Vineesh Indira Chandran, Erika Bourseau-Guilmain, Dmitry Shevela, Jon Lidfeldt, Ann-Sofie Månsson, Silvia Pastorekova, Johannes Messinger, Mattias Belting
Aggressive cancers are characterized by hypoxia, which is a key driver of tumor development and treatment resistance. Proteins specifically expressed in the hypoxic tumor microenvironment thus represent interesting candidates for targeted drug delivery strategies. Carbonic anhydrase (CAIX) has been identified as an attractive treatment target as it is highly hypoxia specific and expressed at the cell-surface to promote cancer cell aggressiveness. Here, we find that cancer cell internalization of CAIX is negatively regulated by post-translational modification with chondroitin or heparan sulfate glycosaminoglycan chains...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28939564/the-effects-of-ph-and-pi-on-tension-and-ca-2-sensitivity-of-ventricular-myofilaments-from-the-anoxia-tolerant-painted-turtle
#8
Cornelia E Fanter, Kenneth S Campbell, Daniel E Warren
We aimed to determine how increases in intracellular H(+) and inorganic phosphate (Pi) to levels observed during anoxic submergence affect contractility in ventricular muscle of the anoxia-tolerant Western painted turtle, Chrysemys picta bellii Skinned multicellular preparations were exposed to six treatments with physiologically relevant levels of pH (7.4, 7.0, 6.6), and Pi (3 mM and 8 mM). Each preparation was tested in a range of calcium concentrations (pCa 9.0-pCa 4.5) to determine the pCa-tension relationship for each treatment...
September 22, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28928268/mild-acidosis-delays-neutrophil-apoptosis-via-multiple-signaling-pathways-and-acts-in-concert-with-inflammatory-mediators
#9
Driss El Kebir, Everton de Oliveira Lima Dos Santos, Soukaina Mansouri, Meriem Sekheri, János G Filep
Accumulating evidence indicates development of local extracellular acidosis in inflamed tissues in response to infection and tissue injury. Activation of infiltrating neutrophils contributes to a transient decrease in pH, which, in turn, triggers innate immunity. In this study, we investigated the impact of extracellular acidosis on neutrophil apoptosis, a critical determinant of the outcome of the inflammatory response and analyzed the underlying signaling pathways. Culture of human isolated neutrophils in mildly acidotic conditions (pH 6...
September 19, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28859158/metabolic-inhibition-reduces-cardiac-l-type-ca2-channel-current-due-to-acidification-caused-by-atp-hydrolysis
#10
Giedrius Kanaporis, Rimantas Treinys, Rodolphe Fischmeister, Jonas Jurevičius
Metabolic stress evoked by myocardial ischemia leads to impairment of cardiac excitation and contractility. We studied the mechanisms by which metabolic inhibition affects the activity of L-type Ca2+ channels (LTCCs) in frog ventricular myocytes. Metabolic inhibition induced by the protonophore FCCP (as well as by 2,4- dinitrophenol, sodium azide or antimycin A) resulted in a dose-dependent reduction of LTCC current (ICa,L) which was more pronounced during β-adrenergic stimulation with isoprenaline. ICa,L was still reduced by metabolic inhibition even in the presence of 3 mM intracellular ATP, or when the cell was dialysed with cAMP or ATP-γ-S to induce irreversible thiophosphorylation of LTCCs, indicating that reduction in ICa,L is not due to ATP depletion and/or reduced phosphorylation of the channels...
2017: PloS One
https://www.readbyqxmd.com/read/28831253/endocytotic-uptake-of-hpma-based-polymers-by-different-cancer-cells-impact-of-extracellular-acidosis-and-hypoxia
#11
Daniel Gündel, Mareli Allmeroth, Sarah Reime, Rudolf Zentel, Oliver Thews
BACKGROUND: Polymeric nanoparticles allow to selectively transport chemotherapeutic drugs to the tumor tissue. These nanocarriers have to be taken up into the cells to release the drug. In addition, tumors often show pathological metabolic characteristics (hypoxia and acidosis) which might affect the polymer endocytosis. MATERIALS AND METHODS: Six different N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer structures (homopolymer as well as random and block copolymers with lauryl methacrylate containing hydrophobic side chains) varying in molecular weight and size were analyzed in two different tumor models...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28827372/monocarboxylate-transporter-mct1-promotes-tumor-metastasis-independently-of-its-activity-as-a-lactate-transporter
#12
Valéry L Payen, Myriam Y Hsu, Kristin S Rädecke, Elisabeth Wyart, Thibaut Vazeille, Caroline Bouzin, Paolo E Porporato, Pierre Sonveaux
Extracellular acidosis resulting from intense metabolic activities in tumors promotes cancer cell migration, invasion, and metastasis. Although host cells die at low extracellular pH, cancer cells resist, as they are well equipped with transporters and enzymes to regulate intracellular pH homeostasis. A low extracellular pH further activates proteolytic enzymes that remodel the extracellular matrix to facilitate cell migration and invasion. Monocarboxylate transporter MCT1 is a passive transporter of lactic acid that has attracted interest as a target for small-molecule drugs to prevent metastasis...
October 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28754162/sensitization-of-asic3-by-proteinase-activated-receptor-2-signaling-contributes-to-acidosis-induced-nociception
#13
Jing Wu, Ting-Ting Liu, Yi-Mei Zhou, Chun-Yu Qiu, Ping Ren, Ming Jiao, Wang-Ping Hu
BACKGROUND: Tissue acidosis and inflammatory mediators play critical roles in pain. Pro-inflammatory agents trypsin and tryptase cleave and activate proteinase-activated receptor 2 (PAR2) expressed on sensory nerves, which is involved in peripheral mechanisms of inflammation and pain. Extracellular acidosis activates acid-sensing ion channel 3 (ASIC3) to trigger pain sensation. Here, we show that a functional interaction of PAR2 and ASIC3 could contribute to acidosis-induced nociception...
July 28, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28727929/na-h-exchanger-and-proton-channel-in-heart-failure-associated-with-becker-and-duchenne-muscular-dystrophies
#14
Ghassan Bkaily, Danielle Jacques
Cardiomyopathy is found in patients with Duchenne (DMD) and Becker (BMD) muscular dystrophies, which are linked muscle diseases caused by mutations in the dystrophin gene. Dystrophin defects are not limited to DMD but are also present in mild BMD. The hereditary cardiomyopathic hamster of the UM-X7.1 strain is a particular experimental model of heart failure (HF) leading to early death in muscular dystrophy (dystrophin deficiency and sarcoglycan mutation) and heart disease (δ-sarcoglycan deficiency and dystrophin mutation) in human DMD...
October 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28631600/inhibition-of-carbonic-anhydrase-ix-by-ureidosulfonamide-inhibitor-u104-reduces-prostate-cancer-cell-growth-but-does-not-modulate-daunorubicin-or-cisplatin-cytotoxicity
#15
Anne Riemann, Antje Güttler, Verena Haupt, Henri Wichmann, Sarah Reime, Matthias Bache, Dirk Vordermark, Oliver Thews
Carbonic anhydrase IX has emerged as a promising target for cancer therapy. It is highly up-regulated in hypoxic regions and mediates pH regulation critical for tumor cell survival as well as extracellular acidification of the tumor microenvironment which promotes tumor aggressiveness via various mechanisms, such as augmenting metastatic potential. Therefore, the aim of this study was to analyze the complex interdependency between CA IX and the tumor microenvironment in prostate tumor cells in concern of potential therapeutic implications...
June 19, 2017: Oncology Research
https://www.readbyqxmd.com/read/28627686/hypoxia-and-acidosis-driven-aberrations-of-secreted-micrornas-in-endometrial-cancer-in-vitro
#16
Julia Eismann, Marc Hirschfeld, Thalia Erbes, Gerta Rücker, Markus Jäger, Andrea Ritter, Daniela Weiss, Gerald Gitsch, Sebastian Mayer
Due to their post-transcriptional regulatory impact on gene expression, microRNAs (miRNA, miRs) influence decisively cellular processes of differentiation, proliferation and apoptosis. In oncogenic pathways various miRNAs exert either oncogenic or tumor suppressor activities in a stage-specific manner. Dysregulation of miRNA expression pattern has been associated with several human cancers including endometrial cancer (EC). In the present study, expression profile alterations of EC associated secreted miRNAs were determined under the microenvironmental stress situations hypoxia and acidosis occurring in tumor progression and metastasis...
June 13, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28605830/sustained-intracellular-acidosis-triggers-the-na%C3%A2-%C2%BA-h%C3%A2-%C2%BA-exchager-1-activation-in-glutamate-excitotoxicity
#17
Bo Kyung Lee, Yi-Sook Jung
The Na⁺/H⁺ exchanger-1 (NHE-1) is a ubiquitously expressed pH-regulatory membrane protein that functions in the brain, heart, and other organs. It is increased by intracellular acidosis through the interaction of intracellular H⁺ with an allosteric modifier site in the transport domain. In the previous study, we reported that glutamate-induced NHE-1 phosphorylation mediated by activation of protein kinase C-β (PKC-β) in cultured neuron cells via extracellular signal-regulated kinases (ERK)/p90 ribosomal s6 kinases (p90RSK) pathway results in NHE-1 activation...
November 1, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28455244/got1-mediated-anaplerotic-glutamine-metabolism-regulates-chronic-acidosis-stress-in-pancreatic-cancer-cells
#18
Jaime Abrego, Venugopal Gunda, Enza Vernucci, Surendra K Shukla, Ryan J King, Aneesha Dasgupta, Gennifer Goode, Divya Murthy, Fang Yu, Pankaj K Singh
The increased rate of glycolysis and reduced oxidative metabolism are the principal biochemical phenotypes observed in pancreatic ductal adenocarcinoma (PDAC) that lead to the development of an acidic tumor microenvironment. The pH of most epithelial cell-derived tumors is reported to be lower than that of plasma. However, little is known regarding the physiology and metabolism of cancer cells enduring chronic acidosis. Here, we cultured PDAC cells in chronic acidosis (pH 6.9-7.0) and observed that cells cultured in low pH had reduced clonogenic capacity...
August 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28445864/tumor-antigen-glycosaminoglycan-modification-regulates-antibody-drug-conjugate-delivery-and-cytotoxicity
#19
Helena C Christianson, Julien A Menard, Vineesh Indira Chandran, Erika Bourseau-Guilmain, Dmitry Shevela, Jon Lidfeldt, Ann-Sofie Månsson, Silvia Pastorekova, Johannes Messinger, Mattias Belting
Aggressive cancers are characterized by hypoxia, which is a key driver of tumor development and treatment resistance. Proteins specifically expressed in the hypoxic tumor microenvironment thus represent interesting candidates for targeted drug delivery strategies. Carbonic anhydrase (CAIX) has been identified as an attractive treatment target as it is highly hypoxia specific and expressed at the cell-surface to promote cancer cell aggressiveness. Here, we find that cancer cell internalization of CAIX is negatively regulated by post-translational modification with chondroitin or heparan sulfate glycosaminoglycan chains...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28393692/nanostructures-for-ph-sensitive-drug-delivery-and-magnetic-resonance-contrast-enhancement-systems
#20
Xiao Sun, Guilong Zhang, Zhengyan Wu
According to the differences of microenvironments between tumors and healthy tissues, if the anticancer drugs or magnetic resonance contrast agents (MRCAs) can be controlled to precisely match physiological needs at targeted tumor sites, it is expected to acquire better therapeutic efficacy and more accurate diagnosis. Over the decade, stimuli-responsive nanomaterials have been a research hotspot for cancer treatment and diagnosis because they show many excellent functions, such as in vivo imaging, combined targeting drug delivery and systemic controlled release, extended circulation time, etc...
April 6, 2017: Current Medicinal Chemistry
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