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Intracellular acidosis

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https://www.readbyqxmd.com/read/28445864/tumor-antigen-glycosaminoglycan-modification-regulates-antibody-drug-conjugate-delivery-and-cytotoxicity
#1
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
#2
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
https://www.readbyqxmd.com/read/28359367/nutritional-regulation-of-coupling-factor-6-a-novel-vasoactive-and-proatherogenic-peptide
#3
REVIEW
Tomohiro Osanai, Kasumi Mikami, Maiko Kitajima, Mayumi Urushizaka, Kumiko Kawasaki, Toshiko Tomisawa, Chieko Itaki, Yuka Noto, Koji Magota, Hirofumi Tomita
High sodium, high glucose, and obesity are important risk factors for age-related diseases such as cardiovascular disease (CVDs), stroke, and cancer. Coupling factor 6 (CF6) is released from vascular endothelial cells and functions as a circulating peptide that inhibits prostacyclin and nitric oxide generation by intracellular acidosis. High glucose elevates CF6 by activation of protein kinase C and p38 mitogen-activated protein kinase, whereas CF6 causes type 2 diabetes mellitus, resulting in a high glucose vicious cycle...
May 2017: Nutrition
https://www.readbyqxmd.com/read/28339694/regional-acidosis-locally-inhibits-but-remotely-stimulates-ca2-waves-in-ventricular-myocytes
#4
Kerrie L Ford, Emma L Moorhouse, Mario Bortolozzi, Mark Richards, Pawel Swietach, Richard D Vaughan-Jones
AIMS: Spontaneous Ca2+ waves in cardiomyocytes are potentially arrhythmogenic. A powerful controller of Ca2+ waves is the cytoplasmic H+ concentration ([H+]i), which fluctuates spatially and temporally in conditions such as myocardial ischaemia/reperfusion. H+-control of Ca2+ waves is poorly understood. We have therefore investigated how [H+]i co-ordinates their initiation and frequency. METHODS AND RESULTS: Spontaneous Ca2+ waves were imaged (fluo-3) in rat isolated ventricular myocytes, subjected to modest Ca2+-overload...
February 21, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28333070/evaluation-of-mct1-mct4-and-cd147-genes-in-peripheral-blood-cells-of-breast-cancer-patients-and-their-potential-use-as-diagnostic-and-prognostic-markers
#5
Maria Cláudia de B Luz, Matheus M Perez, Ligia A Azzalis, Luiz Vinícius de A Sousa, Fernando Adami, Fernando L A Fonseca, Beatriz da C A Alves
BACKGROUND: Patients with breast cancer-the deadliest cancer among women-are at constant risk of developing metastasis. Oxidative stress and hypoxia are common feature of tumor cells that can proliferate even in a resultant metabolic acidosis. Despite the low extracellular pH, intracellular pH of tumor cells remains relatively normal, or even more alkaline due to the action of a membrane protein family known as monocarboxylate transporters (MCTs). The objective of this study was to verify the diagnostic and prognostic value of MCT1, MCT4 and CD147 in tumor and peripheral blood samples of patients with breast cancer undergoing chemotherapic treatment...
March 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28332558/multiple-h-sensors-mediate-the-extracellular-acidification-induced-ca-2-i-elevation-in-cultured-rat-ventricular-cardiomyocytes
#6
Yuan-Lang Hu, Xue Mi, Chao Huang, Hui-Fang Wang, Jian-Ren Song, Qing Shu, Lan Ni, Jian-Guo Chen, Fang Wang, Zhuang-Li Hu
Acidosis has been known to cause "Ca(2+) transients", however, the mechanism is still uncertain. Here, we demonstrated that multiple H(+) sensors, such as ASICs, TRPV1 and proton-sensing G protein coupled receptors (GPCRs) are involved in extracellular acidification-induced intracellular calcium ([Ca(2+)]i) elevation. By using calcium imaging measures, we observed that both ASIC and TRPV1 channels inhibitors suppressed the [Ca(2+)]i elevation induced by extracellular acidosis in cultured rat cardiac myocytes...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28319329/extracellular-acidosis-and-very-low-na-inhibit-nbcn1-and-nhe1-mediated-net-acid-extrusion-from-mouse-vascular-smooth-muscle-cells
#7
Lisbeth Bonde, Ebbe Boedtkjer
AIM: The electroneutral Na(+) ,HCO3(-) -cotransporter NBCn1 and Na(+) /H(+) -exchanger NHE1 regulate acid-base balance in vascular smooth muscle cells (VSMCs) and modify artery function and structure. Pathological conditions-notably ischemia-can dramatically perturb intracellular (i) and extracellular (o) pH and [Na(+) ]. We examined effects of low [Na(+) ]o and pHo on NBCn1 and NHE1 activity in VSMCs of small arteries. METHODS: We measured pHi by 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein-based fluorescence microscopy of mouse mesenteric arteries and induced intracellular acidification by NH4(+) -prepulse technique...
March 20, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28315119/alterations-of-mg-2-after-hemorrhagic-shock
#8
Mun-Young Lee, Dong Kwon Yang, Shang-Jin Kim
Hemorrhagic shock is generally characterized by hemodynamic instability with cellular hypoxia and diminishing cellular function, resulting from an imbalance between systemic oxygen delivery and consumption and redistribution of fluid and electrolytes. Magnesium (Mg) is the fourth most abundant cation overall and second most abundant intracellular cation in the body and an essential cofactor for the energy production and cellular metabolism. Data for blood total Mg (tMg; free-ionized, protein-bound, and anion-bound forms) and free Mg(2+) levels after a traumatic injury are inconsistent and only limited information is available on hemorrhagic effects on free Mg(2+) as the physiologically active form...
March 17, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28298360/stimulation-of-fibroblast-growth-factor-23-by-metabolic-acidosis-requires-osteoblastic-intracellular-calcium-signaling-and-prostaglandin-synthesis
#9
Nancy S Krieger, David A Bushinsky
Serum fibroblast growth factor 23 (FGF23) increases progressively in chronic kidney disease (CKD) and is associated with increased mortality. FGF23 is synthesized in osteoblasts and osteocytes; however, the factors regulating its production are not clear. Patients with CKD have decreased renal acid excretion leading to metabolic acidosis (MET). During MET, acid is buffered by bone with release of mineral calcium (Ca) and phosphate (P). MET increases intracellular Ca signaling and cyclooxygenase 2 (COX2)-induced prostaglandin production in the osteoblast leading to decreased bone formation and increased bone resorption...
March 15, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28293240/extracellular-acidification-inhibits-the-ros-dependent-formation-of-neutrophil-extracellular-traps
#10
Martina Behnen, Sonja Möller, Antonia Brozek, Matthias Klinger, Tamás Laskay
The inflammatory microenvironment is commonly characterized by extracellular acidosis (pH < 7.35). Sensitivity to pH, CO2 or bicarbonate concentrations allows neutrophils to react to changes in their environment and to detect inflamed areas in the tissue. One important antimicrobial effector mechanism is the production of neutrophil extracellular traps (NETs), which are released during a programmed reactive oxygen species (ROS)-dependent cell death, the so-called NETosis. Although several functions of neutrophils have been analyzed under acidic conditions, the effect of extracellular acidosis on NETosis remains mainly unexplored and the available experimental results are contradictory...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28283796/white-sturgeon-acipenser-transmontanus-acid-base-regulation-differs-in-response-to-different-types-of-acidoses
#11
Ryan B Shartau, Dan W Baker, Colin J Brauner
White sturgeon (Acipenser transmontanus) completely protect intracellular tissue pH (pHi) despite large reductions in extracellular (blood) pH (pHe), termed preferential pHi regulation, in response to elevated environmental PCO2 (hypercarbia) and in general appear to be relatively resilient to stressors. Preferential pHi regulation is thought to be associated with hypercarbia tolerance in general, but has also recently been observed to protect pHi against metabolic acidoses induced by exhaustive exercise and anoxia in a tropical air breathing catfish...
March 11, 2017: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
https://www.readbyqxmd.com/read/28276300/value-of-renal-biopsy-in-diagnosing-infantile-nephropathic-cystinosis-associated-with-secondary-nephrogenic-diabetes-insipidus
#12
Emily Joyce, Jacqueline Ho, Areeg El-Gharbawy, Cláudia M Salgado, Sarangarajan Ranganathan, Miguel Reyes-Múgica
Cystinosis is the most common cause of inherited renal Fanconi syndrome in young children, and typically presents with laboratory findings of a proximal tubulopathy and corneal crystals by one year of age. We describe here renal biopsy findings in a 20-month-old patient with an atypical presentation of distal renal tubular acidosis, diabetes insipidus, and the absence of corneal crystals. Although renal biopsy is usually not necessary to establish the diagnosis of cystinosis, when the patient presents with atypical signs and symptoms, a renal biopsy may be extremely valuable...
January 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28270749/identifying-candidate-genes-that-underlie-cellular-ph-sensitivity-in-serotonin-neurons-using-transcriptomics-a-potential-role-for-kir5-1-channels
#13
Madeleine M Puissant, Gary C Mouradian, Pengyuan Liu, Matthew R Hodges
Ventilation is continuously adjusted by a neural network to maintain blood gases and pH. Acute CO2 and/or pH regulation requires neural feedback from brainstem cells that encode CO2/pH to modulate ventilation, including but not limited to brainstem serotonin (5-HT) neurons. Brainstem 5-HT neurons modulate ventilation and are stimulated by hypercapnic acidosis, the sensitivity of which increases with increasing postnatal age. The proper function of brainstem 5-HT neurons, particularly during post-natal development is critical given that multiple abnormalities in the 5-HT system have been identified in victims of Sudden Infant Death Syndrome...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28223003/treatment-of-metformin-intoxication-complicated-by-lactic-acidosis-and-acute-kidney-injury-the-role-of-prolonged-intermittent-hemodialysis
#14
Giuseppe Regolisti, Riccardo Antoniotti, Filippo Fani, Paolo Greco, Enrico Fiaccadori
Metformin intoxication with lactic acidosis, a potentially lethal condition, may develop in diabetic patients when the drug dose is inappropriate and/or its clearance is reduced. Diagnosis and therapy may be delayed due to nonspecific symptoms at presentation, with severe anion gap metabolic acidosis and elevated serum creatinine values being the most prominent laboratory findings. Confirmation requires measurement of serum metformin by high-performance liquid chromatography-tandem mass spectrometry, but this technique is available only at specialized institutions and cannot be relied on as a guide to immediate treatment...
February 17, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28174682/glucose-deprivation-regulates-the-progranulin-sortilin-axis-in-pc12-cells
#15
Ken-Ichi Kawashima, Yuri Ishiuchi, Miki Konnai, Saori Komatsu, Hitoshi Sato, Hideo Kawaguchi, Nobumitsu Miyanishi, Jérôme Lamartine, Masugi Nishihara, Taku Nedachi
Progranulin (PGRN) is a growth factor implicated in several neurodegenerative diseases, such as frontotemporal lobar degeneration. Despite its important role in the central nervous system (CNS), the mechanisms controlling PGRN expression in the CNS are largely unknown. Recent evidence, however, suggested that several stressors, such as hypoxia, acidosis, or oxidative stress, induce PGRN expression. The present study was mainly aimed at determining whether and, if so, how glucose deprivation affects PGRN expression in PC12 cells...
February 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28134630/polyamines-preserve-connexin-43-mediated-gap-junctional-communication-during-intracellular-hypercalcemia-and-acidosis
#16
Lilia Y Kucheryavykh, Jan Benedikt, Luis A Cubano, Serguei N Skatchkov, Feliksas F Bukauskas, Yuriy V Kucheryavykh
Changes in the regulation, formation, and gating of connexin-based gap junction channels occur in various disorders. It has been shown that H and Ca are involved in the regulation of gap junctional communication. Ischemia-induced intracellular acidification and Ca overload lead to closure of gap junctions and inhibit an exchange by ions and small molecules throughout the network of cells in the heart, brain, and other tissues. In this study, we examined the role of the polyamines in the regulation of connexin 43 (Cx43)-based gap junction channels under elevated intracellular concentrations of hydrogen ([H]i) and calcium ([Ca]i) ions...
March 1, 2017: Neuroreport
https://www.readbyqxmd.com/read/28122261/triple-edged-therapy-targeting-intracellular-alkalosis-and-extracellular-acidosis-in-cancer
#17
REVIEW
Tomas Koltai
Extracellular acidity and intracellular alkalinity are two of the characteristics hallmarks of malignant cells and their environment. This involves an inversion of the extracellular/intracellular pH gradient when compared with normal cells and it gives malignant cells proliferative and invasive advantages. Thus, the reversal of the pH gradient is a legitimate objective in the treatment of cancer and may be accomplished with drugs already used for other purposes and/or with specific new drugs that are currently being studied...
January 22, 2017: Seminars in Cancer Biology
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
#18
Fu Liang Ng, Ebbe Boedtkjer, Kate 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...
March 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28066811/ph-dependent-cellular-internalization-of-paramagnetic-nanoparticle
#19
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
#20
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
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