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Intracellular acidosis

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https://www.readbyqxmd.com/read/28087731/increased-nbcn1-expression-na-hco3-co-transport-and-intracellular-ph-in-human-vascular-smooth-muscle-cells-with-a-risk-allele-for-hypertension
#1
Fu Liang Ng, Ebbe Boedtkjer, Katarzyna Witkowska, Meixia Ren, Ruoxin Zhang, Arthur Tucker, Christian Aalkjær, Mark J Caulfield, Shu Ye
Genome-wide association studies have revealed an association between variation at the SLC4A7 locus and blood pressure. SLC4A7 encodes the electroneutral Na(+)/HCO3 co-transporter NBCn1 which regulates intracellular pH (pHi). We conducted a functional study of variants at this locus in primary cultures of vascular smooth muscle and endothelial cells. In both cell types, we found genotype-dependent differences for rs13082711 in DNA-nuclear protein interactions, where the risk allele is associated with increased SLC4A7 expression level, NBCn1 availability and function as reflected in elevated steady-state pHi and accelerated recovery from intracellular acidosis...
January 13, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28066811/ph-dependent-cellular-internalization-of-paramagnetic-nanoparticle
#2
Branislava Janic, Mohammed Pi Bhuiyan, James R Ewing, Meser M Ali
A hallmark of the tumor microenvironment in malignant tumor is extracellular acidosis, which can be exploited for targeted delivery of drugs and imaging agents. A pH sensitive paramagnetic nanoaparticle (NP) is developed by incorporating GdDOTA-4AmP MRI contrast agent and pHLIP (pH Low Insertion Peptide) into the surface of a G5-PAMAM dendrimer. pHLIP showed pH-selective insertion and folding into cell membranes, but only in acidic conditions. We demonstrated that pHLIP-conjugated Gd44-G5 paramagnetic nanoparticle binds and fuses with cellular membrane at low pH, but not at normal physiological pH, and that it promotes cellular uptake...
August 26, 2016: ACS Sensors
https://www.readbyqxmd.com/read/28062849/interplay-between-a-cytosolic-and-a-cell-surface-carbonic-anhydrase-in-ph-homeostasis-and-acid-tolerance-of-leishmania
#3
Dhiman Sankar Pal, Mazharul Abbasi, Dipon Kumar Mondal, Binitha Anu Varghese, Ritama Paul, Shalini Singh, Rupak Datta
Leishmania parasites have evolved to endure the acidic phagolysosomal environment within host macrophages. How Leishmania cells maintain near-neutral intracellular pH and proliferate in such proton-rich milieu remains poorly understood. We report here that for thriving in acidic condition Leishmania major relies on a cytosolic and a cell surface carbonic anhydrase viz. LmCA1 and LmCA2. Upon exposure to acidic medium, intracellular pH of the LmCA1(+/-), LmCA2(+/-) and LmCA1(+/-): LmCA2(+/-) mutant strains dropped by varying extents that led to cell cycle delay, growth retardation and morphological abnormalities...
January 6, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28058990/restoration-of-the-response-of-the-middle-cerebral-artery-of-the-rat-to-acidosis-in-hyposmotic-hyponatremia-by-the-opener-of-large-conductance-calcium-sensitive-potassium-channels-bkca
#4
Marta Aleksandrowicz, Beata Dworakowska, Krzysztof Dolowy, Ewa Kozniewska
Hyposmotic hyponatremia (the decrease of extracellular concentration of sodium ions from 145 to 121 mM and the decrease of hyposmolality from 300 to 250 mOsm/kg H2O) impairs response of the middle cerebral artery (MCA) to acetylcholine and NO donor (S-nitroso-N-acetyl-DL-penicillamine). Since acidosis activates a similar intracellular signaling pathway, the present study was designed to verify the hypothesis that the response of the MCA to acidosis is impaired during acute hyposmotic hyponatremia due to abnormal NO-related signal transduction in vascular smooth muscle cells...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28055960/-genetic-disruption-of-the-phi-regulating-proteins-na-h-exchanger-1-slc9a1-and-carbonic-anhydrase-9-severely-reduces-growth-of-colon-cancer-cells
#5
Scott K Parks, Yann Cormerais, Jerome Durivault, Jacques Pouyssegur
Hypoxia and extracellular acidosis are pathophysiological hallmarks of aggressive solid tumors. Regulation of intracellular pH (pHi) is essential for the maintenance of tumor cell metabolism and proliferation in this microenvironment and key proteins involved in pHi regulation are of interest for therapeutic development. Carbonic anhydrase 9 (CA9) is one of the most robustly regulated proteins by the hypoxia inducible factor (HIF) and contributes to pHi regulation. Here, we have investigated for the first time, the role of CA9 via complete genomic knockout (ko) and compared its impact on tumor cell physiology with the essential pHi regulator Na+/H+ exchanger 1 (NHE1)...
December 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/28028936/hypoxia-inducible-factor-1-promotes-chemoresistance-of-lung-cancer-by-inducing-carbonic-anhydrase-ix-expression
#6
Terumasa Sowa, Toshi Menju, Toyofumi F Chen-Yoshikawa, Koji Takahashi, Shigeto Nishikawa, Takao Nakanishi, Kei Shikuma, Hideki Motoyama, Kyoko Hijiya, Akihiro Aoyama, Toshihiko Sato, Makoto Sonobe, Hiroshi Harada, Hiroshi Date
Lung cancer treatment is difficult owing to chemoresistance. Hypoxia-inducible factor 1 (HIF-1) and HIF-1-induced glycolysis are correlated with chemoresistance; however, this is not evident in lung cancer. We investigated the effect of HIF-1α and carbonic anhydrase IX (CAIX), a transmembrane protein neutralizing intracellular acidosis, on chemoresistance and prognosis of lung cancer patients after induction chemoradiotherapy. Associations of HIF-1α, glucose transporter 1 (GLUT1), and CAIX with chemoresistance of lung cancer were investigated using A549 lung cancer cells under normoxia or hypoxia in vitro...
December 28, 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27981578/bicarbonate-sensing-in-mouse-cortical-astrocytes-during-extracellular-acid-base-disturbances
#7
Shefeeq M Theparambil, Zinnia Naoshin, Sabrina Defren, Jana Schmaelzle, Tobias Weber, Hans-Peter Schneider, Joachim W Deitmer
Extracellular acid/base status of the mammalian brain undergoes dynamic changes during many physiological and pathological events. Although intracellular pH of astrocytes responds to the alteration of extracellular acid/base changes, mechanisms mediating these changes have remained unresolved. We have previously shown that electrogenic sodium bicarbonate cotransporter, NBCe1, is a high-affinity bicarbonate carrier in cortical astrocytes (Theparambil et al 2014). In the present study, we investigated whether NBCe1 plays a role in bicarbonate sensing in astrocytes, and in determining the pHi responses to extracellular acid/base challenges...
December 16, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27981484/uric-acid-is-protective-after-cerebral-ischemia-reperfusion-in-hyperglycemic-mice
#8
Carles Justicia, Angélica Salas-Perdomo, Isabel Pérez-de-Puig, Lisette H Deddens, Geralda A F van Tilborg, Clara Castellví, Rick M Dijkhuizen, Ángel Chamorro, Anna M Planas
Hyperglycemia at stroke onset is associated with poor long-term clinical outcome in numerous studies. Hyperglycemia induces intracellular acidosis, lipid peroxidation, and peroxynitrite production resulting in the generation of oxidative and nitrosative stress in the ischemic tissue. Here, we studied the effects of acute hyperglycemia on in vivo intercellular adhesion molecule-1 (ICAM-1) expression, neutrophil recruitment, and brain damage after ischemia/reperfusion in mice and tested whether the natural antioxidant uric acid was protective...
December 15, 2016: Translational Stroke Research
https://www.readbyqxmd.com/read/27956901/spontaneous-tumour-lysis-syndrome-in-a-multiple-myeloma
#9
Can Huzmeli, Eylem Eliacik, Mustafa Saglam, Baris Doner, Ferhan Candan
The tumor lysis syndrome (TLS) is a collection of metabolic abnormalities that occur in consequence of the release of intracellular contents following lysis of tumor cells. TLS occurs spontaneously or after chemotherapy. Spontaneous TLS is uncommon occurrence in multiple myeloma (MM). We define a case of a 70-year-old woman patient who was found to have MM with spontaneous TLS, following a compression fracture of the T-12 vertebrae. While serum uric acid and phosphorous levels were high, low calcium levels were identified...
2016: Case Reports in Medicine
https://www.readbyqxmd.com/read/27939862/a-quick-reference-on-respiratory-acidosis
#10
REVIEW
Rebecca A Johnson
Respiratory acidosis, or primary hypercapnia, occurs when carbon dioxide production exceeds elimination via the lung and is mainly owing to alveolar hypoventilation. Concurrent increases in Paco2, decreases in pH and compensatory increases in blood HCO3(-) concentration are associated with respiratory acidosis. Respiratory acidosis can be acute or chronic, with initial metabolic compensation to increase HCO3(-) concentrations by intracellular buffering. Chronic respiratory acidosis results in longer lasting increases in renal reabsorption of HCO3(-)...
December 8, 2016: Veterinary Clinics of North America. Small Animal Practice
https://www.readbyqxmd.com/read/27932475/intercalated-cell-depletion-and-vacuolar-h-atpase-mistargeting-in-an-ae1-r607h-knockin-model
#11
Rizwan Mumtaz, Francesco Trepiccione, J Christopher Hennings, Antje K Huebner, Bettina Serbin, Nicolas Picard, A K M Shahid Ullah, Teodor G Păunescu, Diane E Capen, Rawad M Lashhab, Isabelle Mouro-Chanteloup, Seth L Alper, Carsten A Wagner, Emmanuelle Cordat, Dennis Brown, Dominique Eladari, Christian A Hübner
Distal nephron acid secretion is mediated by highly specialized type A intercalated cells (A-ICs), which contain vacuolar H(+)-ATPase (V-type ATPase)-rich vesicles that fuse with the apical plasma membrane on demand. Intracellular bicarbonate generated by luminal H(+) secretion is removed by the basolateral anion-exchanger AE1. Chronically reduced renal acid excretion in distal renal tubular acidosis (dRTA) may lead to nephrocalcinosis and renal failure. Studies in MDCK monolayers led to the proposal of a dominant-negative trafficking mechanism to explain AE1-associated dominant dRTA...
December 8, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27905308/a-case-of-extreme-hypokalaemia
#12
L M Ten Bos, T C Veenstra, B D Westerhof, F H Bosch
Hypokalaemia is a common clinical problem. It can lead to severe disturbances in cardiac, neurological and muscle function. We present the case of a 45-year-old woman who was transported to our hospital with cardiac arrest following ventricular fibrillation. Blood sampling revealed severe acidosis (pH 7.02) and extreme hypokalaemia (0.9 mmol/l). The low serum potassium level was most likely caused by the combination of a very deficient diet and use of a thiazide diuretic. She never reported any symptoms. An acute intracellular shift of potassium due to epinephrine and perhaps also the cathecholamines in Red Bull may have further decreased the serum potassium concentration...
November 2016: Netherlands Journal of Medicine
https://www.readbyqxmd.com/read/27891096/systematic-characterization-of-dynamic-parameters-of-intracellular-calcium-signals
#13
Laurent Mackay, Nicholas Mikolajewicz, Svetlana V Komarova, Anmar Khadra
Dynamic processes, such as intracellular calcium signaling, are hallmark of cellular biology. As real-time imaging modalities become widespread, a need for analytical tools to reliably characterize time-series data without prior knowledge of the nature of the recordings becomes more pressing. The goal of this study is to develop a signal-processing algorithm for MATLAB that autonomously computes the parameters characterizing prominent single transient responses (TR) and/or multi-peaks responses (MPR). The algorithm corrects for signal contamination and decomposes experimental recordings into contributions from drift, TRs, and MPRs...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27876158/is-bicarbonate-therapy-useful
#14
REVIEW
Kate Hopper
Despite concerns about the negative effects of metabolic acidosis, there is minimal evidence that sodium bicarbonate administration is an effective treatment. In addition, sodium bicarbonate therapy is associated with many adverse effects, including paradoxic intracellular acidosis, hypokalemia, hypocalcemia, hypernatremia, and hyperosmolality. Definitive recommendations regarding bicarbonate therapy are challenging as there is little high-quality evidence available. In most clinical scenarios of metabolic acidosis, treatment efforts should focus on resolution of the underlying cause, and sodium bicarbonate therapy should be used with caution, if at all...
November 18, 2016: Veterinary Clinics of North America. Small Animal Practice
https://www.readbyqxmd.com/read/27804847/the-warburg-effect-and-the-hallmarks-of-cancer
#15
Laurent Schwartz, Claudiu T Supuran, Khalid O Alfarouk
It is a longstanding debate whether cancer is one disease or a set of very diverse diseases. The goal of this paper is to suggest strongly that most (if not all) the hallmarks of cancer could be the consequence of the Warburg's effect. As a result of the metabolic impairment of the oxidative phosphorylation, there is a decrease in ATP concentration. To compensate the reduced energy yield, there is massive glucose uptake, anaerobic glycolysis, with an up-regulation of the Pentose Phosphate Pathway resulting in increased biosynthesis leading to increased cell division and local pressure...
October 31, 2016: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/27799782/cancer-fundamentals-behind-ph-targeting-and-the-double-edged-approach
#16
Tomas Koltai
The highly regulated pH of cells and the less-regulated pH of the surrounding extracellular matrix (ECM) is the result of a delicate balance between metabolic processes and proton production, proton transportation, chemical buffering, and vascular removal of waste products. Malignant cells show a pronounced increase in metabolic processes where the 10- to 15-fold rise in glucose consumption is only the tip of the iceberg. Aerobic glycolysis (Warburg effect) is one of the hallmarks of cancer metabolism that implies excessive production of protons, which if stayed inside the cells would result in fatal intracellular acidosis (maintaining a strict acid-base balance is essential for the survival of eukaryotic cells)...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27784676/a-role-for-sodium-chloride-cotransporters-in-the-rapid-regulation-of-ion-uptake-following-acute-environmental-acidosis-new-insights-from-the-zebrafish-model
#17
Raymond W M Kwong, Steve F Perry
The effects of acute exposure to acidic water on Na(+) and Cl(-) homeostasis, and the mechanisms underlying their compensatory regulation, were investigated in the larval zebrafish Danio rerio Exposure to acidic water (pH 4.0; control pH 7.6) for 2 h significantly reduced Na(+) uptake and whole body Na(+) content. Nevertheless, the capacity for Na(+) uptake was substantially increased in fish preexposed to acidic water but measured in control water. Based on the accumulation of the Na(+)-selective dye, Sodium Green, two ionocyte subtypes exhibited intracellular Na(+) enrichment after preexposure to acidic water: H(+)-ATPase rich (HR) cells, which coexpress the Na(+)/H(+) exchanger isoform 3b (NHE3b), and a non-HR cell population...
December 1, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27746861/acid-sensing-ion-channel-1a-regulates-the-survival-of-nucleus-pulposus-cells-in-the-acidic-environment-of-degenerated-intervertebral-discs
#18
Feng Cai, Feng Wang, Xin Hong, Xin-Hui Xie, Rui Shi, Zhi-Yang Xie, Xiao-Tao Wu
OBJECTIVES: Activation of acid-sensing ion channel 1a (ASIC1a) is responsible for tissue injury caused by acidosis in nervous systems. But its physiological and pathological roles in nucleus pulposus cells (NPCs) are unclear. The aim of this study is to investigate whether ASIC1a regulates the survival of NPCs in the acidic environment of degenerated discs. MATERIALS AND METHODS: NPCs were isolated and cultured followed by immunofluorescent staining and Western-blot analysis for ASIC1a...
August 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/27638257/characteristics-of-dairy-cows-with-a-greater-or-lower-risk-of-subacute-ruminal-acidosis-volatile-fatty-acid-absorption-rumen-digestion-and-expression-of-genes-in-rumen-epithelial-cells
#19
X Gao, M Oba
The objective of this study was to examine whether lactating dairy cows with a greater or lower risk of subacute ruminal acidosis (SARA) have differences in volatile fatty acid (VFA) absorption rate, expression of genes involved in VFA metabolism and intracellular pH regulation in rumen epithelial cells, and in situ carbohydrate digestibility in the rumen. We fed 14 ruminally cannulated mid-lactating dairy cows (119 ± 47.2 d in milk; body weight 640 ± 47.9 kg) a high-grain diet consisting of 30% forage ad libitum, with an 18-d diet adaptation and a 7-d sample and data collection period...
September 13, 2016: Journal of Dairy Science
https://www.readbyqxmd.com/read/27633736/adverse-post-resuscitation-myocardial-effects-elicited-by-buffer-induced-alkalemia-ameliorated-by-nhe-1-inhibition-in-a-rat-model-of-ventricular-fibrillation
#20
Lorissa Lamoureux, Jeejabai Radhakrishnan, Thomas G Mason, Jeffrey A Kraut, Raul J Gazmuri
Major myocardial abnormalities occur during cardiac resuscitation including intracellular acidosis - partly caused by CO2 accumulation - and activation of the Na(+)-H(+) exchanger isoform-1 (NHE-1). We hypothesized that a favorable interaction may result from NHE-1 inhibition during cardiac resuscitation followed by administration of a CO2-consuming buffer upon return of spontaneous circulation (ROSC). Ventricular fibrillation was electrically induced in 24 male rats and left untreated for 8 minutes followed by defibrillation after 8 minutes of CPR...
September 15, 2016: Journal of Applied Physiology
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