Organic mercurial diuresis: Inhibition of glutamine utilization in the acidotic rat

1979 ◽  
Vol 57 (3) ◽  
pp. 227-234
Author(s):  
Louise Passerini ◽  
T. C. Welbourne
Keyword(s):  
Glucose Production ◽  
Dry Weight ◽  
Glutamine Metabolism ◽  
Sodium Reabsorption ◽  
Active Sodium ◽  
Reduced Rate ◽  
Glutamine Uptake ◽  
Organic Mercurials ◽  
Isolated Kidneys

Organic mercurials inhibit mitochondrial glutamine metabolism in vitro while metabolic acidosis, a condition in which the predominant renal fuel is glutamine, potentiates mercurial diuresis. The following studies were undertaken to determine whether potentiation of diuresis reflects mercurial inhibition of glutamine utilization.(1) All three mercurials employed (mersalyl, chlormerodrin, and p-chloromercuribenzoate) are diuretics in the rat and this effect was potentiated by NH4Cl.(2) Despite reabsorbing less sodium, mercurial-treated rats had lower kidney ATP content (4.35 ± 0.26 and 3.85 ± 0.43 μmol/g dry weight (mercurial plus NH4Cl)) than did controls (4.95 ± 0.31 and 4.87 ± 0.39 μmol/g dry weight (NH4Cl)).(3) Isolated kidneys from NH4Cl and NH4Cl plus mercurial treated rats were perfused with 1 mML-[U-14C]glutamine to determine rates of extraction and oxidation. Mercurial-treated acidotic rat kidneys had a reduced rate of glutamine uptake (40.8 ± 7.4 vs. 64.8 ± 5.8 μmol/h. per kidney), a diminished rate of glutamine conversion to CO2 (14.8 ± 3.6 vs. 26.4 ± 5.2 μmol/h per kidney), and a reduction in glucose production (16 ± 5 vs. 27 ± 4 μmol/h per kidney). These results are consistent with an effect of organic mercurials upon glutamine utilization, limiting ATP availability, and thereby reducing tubular active sodium reabsorption.

scholarly journals Role of Protein Kinase G in Growth and Glutamine Metabolism of Mycobacterium bovis BCG

2005 ◽  
Vol 187 (16) ◽  
pp. 5852-5856 ◽  
Author(s):  
Liem Nguyen ◽  
Anne Walburger ◽  
Edith Houben ◽  
Anil Koul ◽  
Stefan Muller ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mycobacterium Bovis ◽  
Glutamine Metabolism ◽  
Protein Kinase G ◽  
In Vitro Growth ◽  
Wild Type ◽  
Putative Operon ◽  
Glutamine Uptake

ABSTRACT The survival of pathogenic mycobacteria in macrophages requires the eukaryotic enzyme-like serine/threonine protein kinase G. This kinase with unknown specificity is secreted into the cytosol of infected macrophages and inhibits phagosome-lysosome fusion. The pknG gene is the terminal gene in a putative operon containing glnH, encoding a protein potentially involved in glutamine uptake. Here, we report that the deletion of pknG did not affect either glutamine uptake or intracellular glutamine concentrations. In vitro growth of Mycobacterium bovis BCG lacking pknG was identical to that of the wild type. We conclude that in M. bovis BCG, glutamine metabolism is not regulated by protein kinase G.

scholarly journals ASCT2 (SLC1A5)-dependent glutamine uptake is involved in the progression of head and neck squamous cell carcinoma

2019 ◽  
Vol 122 (1) ◽  
pp. 82-93 ◽  
Author(s):  
Ze Zhang ◽  
Ruoyan Liu ◽  
Yanjie Shuai ◽  
Yuting Huang ◽  
Rui Jin ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Animal Studies ◽  
Neck Squamous Cell Carcinoma ◽  
Glutamine Metabolism ◽  
Glutamine Uptake

Abstract Background Glutamine is an abundant and versatile nutrient in cancer cells. Head and neck squamous cell carcinoma (HNSCC) was reported to be dependent on mainly glucose, not glutamine, for producing the energy required for survival and proliferation. Methods The roles of ASCT2 (SLC1A5) and associated glutamine metabolism were determined by the MTT, colony formation, glutamine uptake, intracellular glutathione, ROS detection, immunofluorescence, immunohistochemistry, and apoptosis enzyme-linked immunosorbent assays as well as animal studies. Results We found that glutamine is also critical for HNSCC. In this study, ASCT2, an amino acid transporter responsible for glutamine transport, in addition to LAT1 and GLS, is overexpressed in HNSCC and associated with poor survival. Using both in vivo and in vitro models, we found that knocking down ASCT2 by shRNAs or miR-137 or the combination of silencing ASCT2 and pharmacologically inhibiting SNAT2 via a small-molecule antagonist called V-9302 significantly suppressed intracellular glutamine levels and downstream glutamine metabolism, including glutathione production; these effects attenuated growth and proliferation, increased apoptosis and autophagy, and increased oxidative stress and mTORC1 pathway suppression in HNSCC. Additionally, silencing ASCT2 improved the response to cetuximab in HNSCC. Conclusions In summary, ASCT2-dependent glutamine uptake and subsequent glutamine metabolism are essential for HNSCC tumorigenesis, and the combination of glutamine uptake inhibitors and cetuximab presents a promising strategy for improving the outcomes of HNSCC patients.

Active transport of iodide by choroid plexus of the rabbit in vitro

1962 ◽  
Vol 202 (4) ◽  
pp. 757-760 ◽  
Author(s):  
Keasley Welch
Keyword(s):  
Choroid Plexus ◽  
Active Transport ◽  
External Medium ◽  
Dry Weight ◽  
Optimal Conditions ◽  
Optimal Function ◽  
Reduced Rate ◽  
Saline Medium

When incubated in vitro in a saline medium containing I131 as iodide, the chloride plexus accumulates this ion. The process by which iodide is transported resembles other extrathyroidal iodide concentrating mechanisms in that it is inhibited by a number of metabolic poisons and by perchlorate, thiocyanate, fluoroborate, fluorosulfonate, difluorophosphate, and nitrate. It depends for optimal function on the presence of oxygen, potassium, and calcium in the external medium, and is able to proceed at a reduced rate in the absence of glucose from the medium. Under optimal conditions approximately 5 x 10–11 moles 1–/mg dry weight/min are accumulated.

Effect of fatty acids on renal ammoniagenesis in in vivo and in vitro studies

1976 ◽  
Vol 231 (3) ◽  
pp. 880-887 ◽  
Author(s):  
P Vinay ◽  
G Lemieux ◽  
P Cartier ◽  
M Ahmad
Keyword(s):  
Fatty Acids ◽  
Glucose Production ◽  
Sodium Palmitate ◽  
Sodium Octanoate ◽  
Acid Base Equilibrium ◽  
Cortical Slices ◽  
Gluconeogenic Substrate ◽  
Glutamine Uptake

Intravenous or renal intra-arterial infusion of sodium octanoate results in a 60% decrease in renal ammoniagenesis in the acidotic dog. Mobilization of endogenous fatty acids by levarterenol infusion is accompanied by a 30% fall in renal ammoniagenesis which coincides with considerable increase in renal extraction of fatty acids. In both types of experiments, the renal extraction of glutamine falls in proportion with decreased ammoniagenesis. The effect of octanoate and levarterenol infusion cannot be explained by changes in acid-base equilibrium, renal hemodynamics, or the release of insulin. In vitro experiments using kidney cortical slices from acidotic dogs show that addition of sodium octanoate (0.05-10 mM) or sodium palmitate (0.1-2.5 mM) to the incubation medium induces a 35% decrease in both ammonia and glucose production when L-glutamine (1 mM) is used as the basic ammoniagenic and gluconeogenic substrate. Glutamine uptake decreases concomitantly, whereas tissue glutamate either rises or remains unchanged. The same results were observed when L-glutamate (5 mM) was used as substrate. Glycerol (5 mM) in the medium has no effect on ammoniagenesis, whereas gluconeogenesis increases by 81%. The present studies demonstrate that fatty acids may interfere with renal ammoniagenesis from glutamine during acidosis. The effect is probably related to substrate availability and competition. Fatty acids appear to inhibit ammoniagenesis in the mitochondria through a direct metabolic effect linked with their oxidation and not through modification of glutamine transport across the mitochondrial membrane.

Metabolic effects of valproate on dog renal cortical tubules

1989 ◽  
Vol 67 (2) ◽  
pp. 88-97 ◽  
Author(s):  
André Gougoux ◽  
Patrick Vinay
Keyword(s):  
Proximal Tubules ◽  
Glutamine Metabolism ◽  
Metabolic Effects ◽  
Lactate Metabolism ◽  
Lactate And Pyruvate ◽  
Lactate Utilization ◽  
Sites Of Action ◽  
Glutamine Uptake ◽  
Stimulation Of

The effect of valproate (0.01–10 mM), an antiepileptic drug inducing hyperammonemia in humans, was studied in vitro on a suspension of renal cortical tubules (> 85% proximal tubules) obtained from six normal dogs. When these tubules were incubated with 1 mM glutamine, the addition of valproate accelerated glutamine uptake, ammoniagenesis, and the production of alanine, lactate, and pyruvate. With 5 mM glutamine, a rise in glutamate accumulation, a much greater synthesis of alanine, an important aspartate production, and a striking accumulation of lactate and pyruvate were observed. With 1 or 5 mM lactate, lactate utilization and gluconeogenesis were markedly reduced with increasing concentrations of valproate. Oxygen consumption was reduced by only 15–20% by 10 mM valproate. The accelerated glutamine utilization resulting from valproate could not be prevented by aminooxyacetate, an inhibitor of transamination. Valproate also reduced various enzymatic activities, a finding that could not explain its metabolic effects. Four sites of action may explain these various metabolic changes: (i) a stimulation of mitochondrial glutamine transport, (ii) an increase in the flux of glutamate to malate, and (iii) a reduction in the net oxidation of pyruvate and (iv) in the flux through pyruvate carboxylase.Key words: hyperammonemia, glutamine metabolism, ammoniagenesis, pyruvate, lactate metabolism.

Characteristics of glutamine metabolism by rat kidney tubules: a carbon and nitrogen balance

1979 ◽  
Vol 57 (4) ◽  
pp. 346-356 ◽  
Author(s):  
Patrick Vinay ◽  
Guy Lemieux ◽  
André Gougoux
Keyword(s):  
Rat Kidney ◽  
Glucose Production ◽  
Glutamine Metabolism ◽  
Kidney Tubules ◽  
Total Oxidation ◽  
Physiological Concentration ◽  
Prolonged Incubation ◽  
Carbon Chains ◽  
Glucose Synthesis

The metabolism of glutamine by a suspension of rat kidney tubules was studied in vitro. The influence of duration of incubation, glutamine concentration, and metabolic state of the donor animals was investigated. The relative importance of glucose synthesis, amino acid production, and oxidation to CO2 was estimated by drawing a complete balance of the nitrogens and the carbon chains of the extracted glutamine. It was found that the initial (first 15 min) rate of glutamine utilization was significantly greater than the subsequent rate due to an initial, but transient, extracellular accumulation of glutamate. This phenomenon was suppressed when a small amount of glutamate was added to the incubation medium. Glucose production constitutes the major fate for glutamine metabolism. No net oxidation of glutamine could be detected with 1 mM glutamine during the first 30 min. However, glutamine oxidation becomes significant after prolonged incubation (16% at 120 min). The metabolic fate of glutamine differs when 5 or 10 mM are presented to the tubules, glutamate production and oxidation to CO2 becoming more important. Metabolic acidosis or a 48-h fast increases glutamine extraction and enhances its utilization towards glucose synthesis while they depress glutamate accumulation and oxidation to CO2. Metabolic alkalosis has the opposite effect. It is concluded that the metabolism of glutamine in vitro is dependent on the conditions of the study. Furthermore, total oxidation to CO2 is not a major fate for glutamine metabolism at physiological concentration and is not enhanced by acidosis in the rat kidney in vitro.

Regulation of the maximum rate of renal ammoniagenesis in the acidotic dog

1985 ◽  
Vol 248 (4) ◽  
pp. F607-F615 ◽  
Author(s):  
M. L. Halperin ◽  
P. Vinay ◽  
A. Gougoux ◽  
C. Pichette ◽  
R. L. Jungas
Keyword(s):  
Venous Blood ◽  
Glucose Production ◽  
Glutamine Metabolism ◽  
Sodium Reabsorption ◽  
Atp Production ◽  
Arterial Blood ◽  
Upper Limit ◽  
Rate Of Oxygen Consumption ◽  
Ammonium Production ◽  
Almost All

Metabolism of glutamine results in the net production of ATP; however, cells cannot sustain an ATP production rate greater than their rate of ATP utilization. The purpose of these studies was to determine whether the rate of ATP turnover in the kidney could set an upper limit on renal glutamine metabolism and thereby renal ammoniagenesis. The acidotic dog kidneys extracted glutamine, lactate, citrate, and oxygen from the arterial blood and added ammonium and alanine to the venous blood. Renal glutamine metabolism was responsible for almost all the ammonium production. Renal ATP production was estimated from the rate of oxygen consumption and appeared to be derived roughly equally from the oxidation of glutamine and lactate. There was no apparent renal glucose production from ATP balance calculations and this impression was supported when the inhibitor of gluconeogenesis, 3-mercaptopicolinate, did not inhibit ammoniagenesis. Approximately 90% of the ATP synthesized was utilized to reabsorb sodium. When the amount of ATP utilized for sodium reabsorption in the proximal convoluted tubule (assumed to be 60% of filtered sodium) was compared with the amount of ATP produced from glutamine metabolism, the values were similar despite the fact that the glomerular filtration rate in individual dogs varied more than fourfold. When the quantity of ATP expended for sodium reabsorption was decreased by the infusion of ouabain or by the constriction of one renal artery without reducing glutamine delivery, the kidney lowered its rate of ammoniagenesis to a quantitatively predictable amount.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of the endophytic plant growth promoting Enterobacter ludwigii EB4B on tomato growth

2020 ◽  
Vol 13 (2) ◽  
pp. 54-65 ◽  
Author(s):  
M.E.A. Bendaha ◽  
H.A. Belaouni
Keyword(s):  
Root Length ◽  
Biocontrol Agent ◽  
Growth Promotion ◽  
Dry Weight ◽  
Antagonistic Activity ◽  
Rrna Gene ◽  
Plant Growth Promoting ◽  
Enterobacter Ludwigii ◽  
Tomato Growth

SummaryThis study aims to develop a biocontrol agent against Fusarium oxysporum f.sp. radicis-lycopersici (FORL) in tomato. For this, a set of 23 bacterial endophytic isolates has been screened for their ability to inhibit in vitro the growth of FORL using the dual plate assay. Three isolates with the most sound antagonistic activity to FORL have been qualitatively screened for siderophore production, phosphates solubilization and indolic acetic acid (IAA) synthesis as growth promotion traits. Antagonistic values of the three candidates against FORL were respectively: 51.51 % (EB4B), 51.18 % (EB22K) and 41.40 % (EB2A). Based on 16S rRNA gene sequence analysis, the isolates EB4B and EB22K were closely related to Enterobacter ludwigii EN-119, while the strain EB2A has been assigned to Leclercia adecarboxylata NBRC 102595. The promotion of tomato growth has been assessed in vitro using the strains EB2A, EB4B and EB22K in presence of the phytopathogen FORL. The treatments with the selected isolates increased significantly the root length and dry weight. Best results were observed in isolate EB4B in terms of growth promotion in the absence of FORL, improving 326.60 % of the root length and 142.70 % of plant dry weight if compared with untreated controls. In the presence of FORL, the strain EB4B improved both root length (180.81 %) and plant dry weight (202.15 %). These results encourage further characterization of the observed beneficial effect of Enterobacter sp. EB4B for a possible use as biofertilizer and biocontrol agent against FORL.

scholarly journals Evaluation of the Antioxidant, Anti-Inflammatory and Cytoprotective Activities of Halophyte Extracts against Mycotoxin Intoxication

Toxins ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 312
Author(s):  
Nolwenn Hymery ◽  
Xavier Dauvergne ◽  
Halima Boussaden ◽  
Stéphane Cérantola ◽  
Dorothée Faugère ◽  
...  
Keyword(s):  
Antioxidant Activities ◽  
Protective Action ◽  
Dry Weight ◽  
Cell Protection ◽  
Natural Habitats ◽  
Total Antioxidant ◽  
Mdbk Cells ◽  
Dpph Scavenging ◽  
T2 Toxin

Twelve halophyte species belonging to different families, widely represented along French Atlantic shoreline and commonly used in traditional medicine, were screened for protective activities against mycotoxins, in order to set out new promising sources of natural ingredients for feed applications. Selected halophytic species from diverse natural habitats were examined for their in vitro anti-mycotoxin activities, through viability evaluation of Madin-Darby Bovine Kidney (MDBK) and intestinal porcine enterocyte (IPEC-J2) cell lines. Besides, the in vitro antioxidant activities of plant extracts were assessed (total antioxidant and 2,2-diphenyl-1-picrylhydrazyl (DPPH)-scavenging bioassays). Of the 12 species, Galium arenarium, Convolvulus soldanella and Eryngium campestre exhibited the most protective action on MDBK and IPEC-J2 cells against zearalenone (ZEN) or T2 toxin contamination (restoring about 75% of cell viability at 10 μg·mL−1) without inflammation response. They also had strong antioxidant capacities (Inhibitory concentration of 50% (IC50) < 100 μg·mL−1 for DPPH radical and total antioxidant capacity (TAC) of 100 to 200 mg Ascorbic Acid Equivalent (AAE)·g−1 Dry Weight), suggesting that cell protection against intoxication involves antioxidant action. A bio-guided study showed that fractions of G. arenarium extract protect MDBK cells against T2 or ZEN toxicity and several major compounds like chlorogenic acid and asperuloside could be involved in this protective effect. Overall, our results show that the halophytes G. arenarium, C. soldanella and E. campestre should be considered further as new sources of ingredients for livestock feed with protective action against mycotoxin intoxication.

scholarly journals In-Vitro Evaluation of the Antioxidant and Anti-Inflammatory Activity of Volatile Compounds and Minerals in Five Different Onion Varieties

Separations ◽  
2021 ◽  
Vol 8 (5) ◽  
pp. 57
Author(s):  
Rokayya Sami ◽  
Abeer Elhakem ◽  
Mona Alharbi ◽  
Manal Almatrafi ◽  
Nada Benajiba ◽  
...  
Keyword(s):  
Volatile Compounds ◽  
Dimethyl Sulfide ◽  
Antioxidant Activities ◽  
Dry Weight ◽  
No Production ◽  
Oxidative Stresses ◽  
Anti Inflammatory ◽  
Red Variety ◽  
A Minor

Onions contain high antioxidants compounds that fight inflammation against many diseases. The purpose was to investigate some selected bioactive activities of onion varieties (Yellow, Red, Green, Leek, and Baby). Antioxidant assays and anti-inflammatory activities such as NO production with the addition of some bioactive components were determined and analyzed by using a spectrophotometer. Gas chromatography and mass spectrometry (GC–MS) was used for the volatile compounds, while an Atomic absorption spectrometer was used for mineral determinations. Red variety achieved the highest antioxidant activities. The total flavonoids were between (12.56 and 353.53 mg Quercetin/gin dry weight) (dw) and the total phenol was (8.75–25.73 mg/g dw). Leek, Yellow and Green extracts achieved highly anti-inflammatory values (3.71–4.01 μg/mL) followed by Red and Baby extracts, respectively. The highest contents of sodium, potassium, zinc, and calcium were established for Red onions. Furfuraldehyde, 5-Methyl-2-furfuraldehyde, 2-Methyl-2-pentenal, and 1-Propanethiol were the most predominant, followed by a minor abundance of the other compounds such as Dimethyl sulfide, Methyl allyl disulfide, Methyl-trans-propenyl-disulfide, and Methyl propyl disulfide. The results recommend that these varieties could act as sources of essential antioxidants and anti-inflammatories to decrease inflammation and oxidative stresses, especially red onions that recorded high activities.

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