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Intracellular acidosis

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https://www.readbyqxmd.com/read/29762478/insulin-sensitivity-and-glucose-homeostasis-can-be-influenced-by-metabolic-acid-load
#1
REVIEW
Lucio Della Guardia, Michael Alex Thomas, Hellas Cena
Recent epidemiological findings suggest that high levels of dietary acid load can affect insulin sensitivity and glucose metabolism. Consumption of high protein diets results in the over-production of metabolic acids which has been associated with the development of chronic metabolic disturbances. Mild metabolic acidosis has been shown to impair peripheral insulin action and several epidemiological findings suggest that metabolic acid load markers are associated with insulin resistance and impaired glycemic control through an interference intracellular insulin signaling pathways and translocation...
May 15, 2018: Nutrients
https://www.readbyqxmd.com/read/29672298/intermittent-hypoxia-inhibits-na-h-exchange-mediated-acid-extrusion-via-intracellular-na-accumulation-in-cardiomyocytes
#2
Huai-Ren Chang, Chih-Feng Lien, Jing-Ren Jeng, Jen-Che Hsieh, Chen-Wei Chang, Jian-Hong Lin, Kun-Ta Yang
BACKGROUND/AIMS: Intermittent hypoxia (IH) has been shown to exert preconditioning-like cardioprotective effects. It also has been reported that IH preserves intracellular pH (pHi) during ischemia and protects cardiomyocytes against ischemic reperfusion injury. However, the exact mechanism is still unclear. METHODS: In this study, we used proton indicator BCECF-AM to analyze the rate of pHi recovery from acidosis in the IH model of rat neonatal cardiomyocytes. Neonatal cardiomyocytes were first treated with repetitive hypoxia-normoxia cycles for 1-4 days...
April 16, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29655915/real-time-monitoring-of-ph-dependent-intracellular-trafficking-of-ovarian-cancer-g-protein-coupled-receptor-1-in-living-leukocytes
#3
Modong Tan, Satoshi Yamaguchi, Motonao Nakamura, Teruyuki Nagamune
G-protein coupled receptors (GPCRs) are involved in many diseases and important biological phenomena; elucidating the mechanisms underlying regulation of their signal transduction potentially provides both novel targets for drug discovery and insight into living systems. A proton-sensing GPCR, ovarian cancer G protein-coupled receptor 1 (OGR1), has been reported to be related to acidosis and diseases that cause tissue acidification, but the mechanism of proton-induced activation of OGR1-mediated signal transduction in acidic conditions remains unclear...
April 11, 2018: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/29560104/coordinate-effects-of-p2x7-and-extracellular-acidification-in-microglial-cells
#4
Ponarulselvam Sekar, Duen-Yi Huang, Shwu-Fen Chang, Wan-Wan Lin
Extracellular adenosine 5'-triphosphate (ATP) is a damage-associated molecular pattern and contributes to inflammation associated diseases including cancer. Extracellular acidosis is a novel danger signal in the inflammatory sites, where it can modulate inflammation, immunity and tumor growth. Extracellular acidification was shown to inhibit P2X7-mediated channel currents, while it remains unknown how acidification and P2X7 together affect cellular responses. Here, we treated BV-2 microglial cells with ATP in a short period (<15 min) or a sustained acidified condition...
February 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29530865/identification-of-structural-and-molecular-features-involved-in-the-transport-of-3-deoxy-nucleoside-analogs-by-human-equilibrative-nucleoside-transporter-3
#5
Md Fazlur Rahman, Radhika Raj, Rajgopal Govindarajan
Combination antiretroviral drug treatments depend on 3'-deoxy-nucleoside analogs such as 3'-azido-3'-deoxythymidine (AZT) and 2'3'-dideoxyinosine (DDI). Despite being effective in inhibiting human immunodeficiency virus replication, these drugs produce a range of toxicities, including myopathy, pancreatitis, neuropathy, and lactic acidosis, that are generally considered as sequelae to mitochondrial damage. Although cell surface-localized nucleoside transporters, such as human equilibrative nucleoside transporter 2 (hENT2) and human concentrative nucleoside transporter 1 (hCNT1), are known to increase the carrier-mediated uptake of 3'-deoxy-nucleoside analogs into cells, another ubiquitously expressed intracellular nucleoside transporter (namely, hENT3) has been implicated in the mitochondrial transport of 3'-deoxy-nucleoside analogs...
May 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29524788/functional-and-molecular-characterization-of-transmembrane-intracellular-ph-regulators-in-human-dental-pulp-stem-cells
#6
Gunng-Shinng Chen, Shiao-Pieng Lee, Shu-Fu Huang, Shih-Chi Chao, Chung-Yi Chang, Gwo-Jang Wu, Chung-Hsing Li, Shih-Hurng Loh
OBJECTIVE: Homeostasis of intracellular pH (pHi ) plays vital roles in many cell functions, such as proliferation, apoptosis, differentiation and metastasis. Thus far, Na+ -H+ exchanger (NHE), Na+ -HCO3 - co-transporter (NBC), Cl- /HCO3 - exchanger (AE) and Cl- /OH- exchanger (CHE) have been identified to co-regulate pHi homeostasis. However, functional and biological pHi -regulators in human dental pulp stem cells (hDPSCs) have yet to be identified. DESIGN: Microspectrofluorimetry technique with pH-sensitive fluorescent dye, BCECF, was used to detect pHi changes...
June 2018: Archives of Oral Biology
https://www.readbyqxmd.com/read/29517989/coordinated-regulation-of-metabolic-transporters-and-migration-invasion-by-carbonic-anhydrase-ix
#7
REVIEW
Paul C McDonald, Mridula Swayampakula, Shoukat Dedhar
Hypoxia is a prominent feature of the tumor microenvironment (TME) and cancer cells must dynamically adapt their metabolism to survive in these conditions. A major consequence of metabolic rewiring by cancer cells in hypoxia is the accumulation of acidic metabolites, leading to the perturbation of intracellular pH (pHi) homeostasis and increased acidosis in the TME. To mitigate the potentially detrimental consequences of an increasingly hypoxic and acidic TME, cancer cells employ a network of enzymes and transporters to regulate pH, particularly the extracellular facing carbonic anhydrase IX (CAIX) and CAXII...
March 8, 2018: Metabolites
https://www.readbyqxmd.com/read/29482687/life-threatening-hypokalemic-quadriplegia-in-a-postoperative-patient
#8
Manoj Kamal, Geeta Singariya, Om Prakash Suthar, Ashwini S
Acute hypokalemic paralysis is a reversible but potentially lethal clinical condition. We report a case, who developed rapidonset quadriparesis in immediate postoperative period after undergoing right percutaneous nephrolithotomy for bilateral renal stones. On evaluation, she was found to have hypernatremic, hyperchloremic, hypokalemic acidosis. This severe hypokalemia-induced quadriparesis was precipitated by repeated furosemide injections, use of potassium-free fluid as maintenance, intracellular shift due to free water administration in this patient, who had pre-existing distal renal tubular acidosis...
March 2018: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
https://www.readbyqxmd.com/read/29461272/does-aerobic-respiration-produce-carbon-dioxide-or-hydrogen-ion-and-bicarbonate
#9
Erik R Swenson
Maintenance of intracellular pH is critical for clinical homeostasis. The metabolism of glucose, fatty acids, and amino acids yielding the generation of adenosine triphosphate in the mitochondria is accompanied by the production of acid in the Krebs cycle. Both the nature of this acidosis and the mechanism of its disposal have been argued by two investigators with a long-abiding interest in acid-base physiology. They offer different interpretations and views of the molecular mechanism of this intracellular pH regulation during normal metabolism...
May 2018: Anesthesiology
https://www.readbyqxmd.com/read/29449648/the-role-of-disease-linked-residue-glutamine-913-in-support-of-the-structure-and-function-of-the-human-electrogenic-sodium-bicarbonate-cotransporter-nbce1-a
#10
Evan J Myers, Aniko Marshall, Mark D Parker
Mutations in the sodium bicarbonate cotransporter NBCe1 (SLC4A4) cause proximal renal tubular acidosis (pRTA). We recently described a novel pRTA mutation p.Gln913Arg (Q913R), inherited in compound heterozygous form with p.Arg510His (R510H). Q913R causes intracellular retention of NBCe1 and a 'gain of function' Cl- leak. To learn more about the importance of glutamine at position 913, we substituted a variety of alternative amino-acid residues (Cys, Glu, Lys, Leu, Ser) at position 913. Studying cRNA-injected Xenopus oocytes by voltage clamp, we find that most de novo mutants exhibit close-to-normal NBCe1 activity; only Q913K expresses a Cl- leak...
February 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29447831/rhabdomyolysis-after-prolonged-surgery-report-of-2-cases-and-review-of-literature
#11
Rebecca Grammer, Jingping Wang, Edward Lahey
Rhabdomyolysis is a condition in which damaged muscle tissue breaks down and intracellular contents, including myoglobin, are released into the circulation. This produces a nonspecific clinical syndrome including electrolyte disturbances, hypovolemia, metabolic acidosis, coagulopathies, and risk of acute kidney injury. Rhabdomyolysis has been reported as a complication of prolonged surgical procedures but has rarely been reported in the oral and maxillofacial surgery literature. Early diagnosis and treatment of rhabdomyolysis are important to avoid long-term complications such as renal failure...
February 2, 2018: Journal of Oral and Maxillofacial Surgery
https://www.readbyqxmd.com/read/29385880/the-effect-of-antioxidants-on-angiogenesis-in-uterine-transplantation
#12
Tugba Ugurlu, Candan Ozogul, Gulistan Sanem Saribas, Seren Gulsen Gurgen, Seda Nur Akyol, Bahar Kartal
The aim of this study was to investigate the effect of antioxidants on angiogenesis in uterine transplantation. We used 24 female rats equally divided into four groups: Group 1 had the uterus stored in HTK (Histidine-Tryptophan-Ketoglutarate) solution at 4 °C cold storage for 4 h. Group 2 had the uterine tissue stored in HTK solution combined with acetyl L-carnitine (10-8  M) for 4 h at +4 °C. The same procedures with Group 1 and 2 were repeated for 24 h for Groups 3 and 4, respectively. Histological investigation and immunohistochemical analysis were performed...
April 2018: Journal of Obstetrics and Gynaecology: the Journal of the Institute of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/29378818/carbonic-anhydrase-expression-in-the-branchial-ionocytes-of-rainbow-trout
#13
Michael Brannen, Kathleen M Gilmour
Rainbow trout ( Oncorhynchus mykiss ) exposed to acid-base challenges activate branchial mechanisms for the excretion of acid-base equivalents. Current models of branchial acid-base excretion in freshwater rainbow trout propose two main ionocyte types: the peanut lectin agglutinin-positive (PNA+ ) mitochondrion-rich cell or ionocyte is believed to secrete HCO3 - in exchange for Cl- , whereas H+ secretion is thought to occur across PNA- ionocytes in exchange for Na+ Both HCO3 - and H+ are supplied by intracellular hydration of CO2 catalysed by cytosolic carbonic anhydrase (CAc)...
March 12, 2018: Journal of Experimental Biology
https://www.readbyqxmd.com/read/29371768/altered-kinetics-properties-of-erythrocyte-lactate-dehydrogenase-in-type-ii-diabetic-patients-and-its-implications-for-lactic-acidosis
#14
Aniket V Mali, Sunita S Bhise, Surendra S Katyare, Mahabaleshwar V Hegde
Recent studies have been noted that the erythrocytes from Type II diabetic patients show significantly altered structural and functional characteristics along with the changed intracellular concentrations of glycolytic intermediates. More recent studies from our laboratory have shown that the activities of enzymes of glycolytic pathway changed significantly in RBCs from Type II diabetic patients. In particular the levels of lactate dehydrogenase (LDH) increased significantly. Lactic acidosis is an established feature of diabetes and LDH plays a crucial role in conversion of pyruvate to lactate and reportedly, the levels of lactate are significantly high which is consistent with our observation on increased levels of LDH...
January 2018: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/29357509/benzolamide-perpetuates-acidic-conditions-during-reperfusion-and-reduces-myocardial-ischemia-reperfusion-injury
#15
Alejandro Ciocci Pardo, Romina G Díaz, Luisa F González Arbeláez, Nestor G Perez, Erik Richard Swenson, Susana M Mosca, Bernardo V Alvarez
During ischemia, increased anaerobic glycolysis results in intracellular acidosis. Activation of alkalinizing transport mechanisms associated with carbonic anhydrases (CA) leads to myocardial intracellular Ca2+ increase. We characterize the effects of inhibition of CA with benzolamide (BZ) during cardiac ischemia-reperfusion (I/R). Langendorff perfused isolated rat hearts were subjected to 30 min of global ischemia and 60 min of reperfusion. Other hearts were treated with BZ (5 μM) during the initial 10 min of reperfusion or perfused with acid solution (AR, pH 6...
December 21, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/29331741/extracellular-acidification-induces-ros-and-mptp-mediated-death-in-hek293-cells
#16
José Teixeira, Farhan Basit, Herman G Swarts, Marleen Forkink, Paulo J Oliveira, Peter H G M Willems, Werner J H Koopman
The extracellular pH (pHe) is a key determinant of the cellular (micro)environment and needs to be maintained within strict boundaries to allow normal cell function. Here we used HEK293 cells to study the effects of pHe acidification (24h), induced by mitochondrial inhibitors (rotenone, antimycin A) and/or extracellular HCl addition. Lowering pHe from 7.2 to 5.8 reduced cell viability by 70% and was paralleled by a decrease in cytosolic pH (pHc), hyperpolarization of the mitochondrial membrane potential (Δψ), increased levels of hydroethidine-oxidizing ROS and stimulation of protein carbonylation...
May 2018: Redox Biology
https://www.readbyqxmd.com/read/29311258/molecular-mechanisms-of-cutis-laxa-and-distal-renal-tubular-acidosis-causing-mutations-in-v-atpase-a-subunits-atp6v0a2-and-atp6v0a4
#17
Sally Esmail, Norbert Kartner, Yeqi Yao, Joo Wan Kim, Reinhart A F Reithmeier, Morris F Manolson
The a subunit is the largest of 15 different subunits that make up the vacuolar H+ -ATPase (V-ATPase) complex, where it functions in proton translocation. In mammals, this subunit has four paralogous isoforms, a 1- a 4, which may encode signals for targeting assembled V-ATPases to specific intracellular locations. Despite the functional importance of the a subunit, its structure remains controversial. By studying molecular mechanisms of human disease-causing missense mutations within a subunit isoforms, we may identify domains critical for V-ATPase targeting, activity and/or regulation...
February 23, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29163059/oxygen-and-glucose-deprivation-induces-bergmann-glia-membrane-depolarization-and-ca-2-rises-mainly-mediated-by-k-and-atp-increases-in-the-extracellular-space
#18
Romain Helleringer, Oana Chever, Hervé Daniel, Micaela Galante
During brain ischemia, intense energy deficiency induces a complex succession of events including pump failure, acidosis and exacerbated glutamate release. In the cerebellum, glutamate is the principal mediator of Purkinje neuron anoxic depolarization during episodes of oxygen and glucose deprivation (OGD). Here, the impact of OGD is studied in Bergmann glia, specialized astrocytes closely associated to Purkinje neurons. Patch clamp experiments reveal that during OGD Bergmann glial cells develop a large depolarizing current that is not mediated by glutamate and purinergic receptors but is mainly due to the accumulation of K+ in the extracellular space...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29132215/in-vivo-molecular-electron-paramagnetic-resonance-based-spectroscopy-and-imaging-of-tumor-microenvironment-and-redox-using-functional-paramagnetic-probes
#19
Valery V Khramtsov
SIGNIFICANCE: A key role of the tumor microenvironment (TME) in cancer progression, treatment resistance, and as a target for therapeutic intervention is increasingly appreciated. Among important physiological components of the TME are tissue hypoxia, acidosis, high reducing capacity, elevated concentrations of intracellular glutathione (GSH), and interstitial inorganic phosphate (Pi). Noninvasive in vivo pO2 , pH, GSH, Pi, and redox assessment provide unique insights into biological processes in the TME, and may serve as a tool for preclinical screening of anticancer drugs and optimizing TME-targeted therapeutic strategies...
December 20, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29101173/ph-recovery-from-a-proton-load-in-rat-cardiomyocytes-effects-of-chronic-exercise
#20
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 and sedentary control rats in CO2 /[Formula: see text]-free media. Acidosis was created by the NH4 Cl prepulse technique, and intracellular pH (pHi ) was determined using fluorescence microscopy on carboxy-SNARF-1 AM-loaded isolated cardiomyocytes. CO2 -independent pHi buffering capacity (βi ) was measured by incrementally reducing the extracellular NH4 Cl concentration in steps of 50% from 20 to 1.25 mM...
February 1, 2018: American Journal of Physiology. Heart and Circulatory Physiology
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