Effects of the nonsteroidal anti-inflammatory drug piroxicam on energy metabolism in the perfused rat liver

• 1.1. The actions of piroxicam, a nonsteroidal and noncarboxylic anti-inflammatory drug, on the metabolism of the isolated perfused rat liver were investigated. The main purpose was to verify if piroxicam is also active on glycogenolysis and energy metabolism, as demonstrated for several carboxylic nonsteroidal anti-inflammatories.
• 2.2. Piroxicam increased oxygen consumption in livers from both fed and fasted rats.
• 3.3. Piroxicam increased glucose release and glycolysis from endogenous glycogen (glycogenolysis).
• 4.4. Gluconeogenesis from lactate plus pyruvate was inhibited.
• 5.5. The action of piroxicam on oxygen consumption was blocked by antimycin A, but not by atractyloside.
• 6.6. The action of piroxicam in the perfused rat liver metabolism seems to be a consequence of its action on mitochondria.
• 7.7. It can be concluded that inhibition of energy metabolism and stimulation of glycogenolysis are not specific properties of carboxylic nonsteroidal anti-inflammatory drugs.

     

Seasonal changes of water,electrolytes and aldosterone levels in blood serum,brain and kidney of the Egyptian cobra “Naja haje haje”

 

• 1.The levels of water, Na, K, Ca and Mg in blood serum, brain and kidney and aldosterone level in blood of Naja haje haje were studied during the different phases of the annual cycle.
• 2.The water content in the tissues studied displayed only minor changes as the animals passed from one phase to the other.
• 3.A significant increase in Na was recorded in the brain during the different phases indicating a depressed sodium pump, whereas the blood Na level showed a significant decrease during hibernation.
• 4.K increased in blood serum, brain and kidney during hibernation, while a nonsignificant decrease was found in blood serum during arousal. The brain may act as a potassium reservoir.
• 5.An increase in Ca and Mg concentration was recorded in blood serum, brain and kidney during prehibernation and hibernation. The data suggested a homeostatic function in the transport and metabolism of these cations.
• 6.Aldosterone exhibited a highly significant decrease especially during hibernation. The aldosterone regulation of ionic composition is discussed.
• 7.Na/K and Ca/Mg ratios in the brain may explain the decreased excitability during winter torpor.

     

The purification of kallikrein from human whole saliva

• 1.1. A quick and simple procedure is described for purifying kallikrein from human whole saliva. The enzyme has been purified about 2700-fold with a yield of approx. 30%.
• 2.2. The procedure is based on the immediate fractionation of saliva by ion exchange chromatography. This is followed by a combination of affinity and high performance liquid chromatography.
• 3.3. The results indicate that another protein component binds to the enzyme at pH 8.0.
• 4.4. The homogeneity of the enzyme has been demonstrated by gel electrophoresis in the absence as well as in the presence of sodium dodecylsulfate.
• 5.5. A mol. wt of 40,100±1800 has been calculated from gel electrophores is experiments.
• 6.6. Sedimentation equilibrium in an analytical ultracentrifuge gave a mol. wt of 39,700.
• 7.7. The amino acid composition has been determined and it confirms that the enzyme has a low isoelectric point.
• 8.8. The presence of tryptophan has been demonstrated by absorption and fluorescence spectroscopy.

     

Occurrence of d-alanine in the eggs and the developing embryo of the sea urchin Paracentrotus lividus

• 1.1. d-Alanine has been found in appreciable amounts in the eggs and embryos of the sea urchin Paracentrotus lividus.
• 2.2. The content of d-alanine, expressed as pmol/egg or embryo, is 1.32 in the egg, 0.81 in the blastula, 0.54 in the gastrula and 0.60 in the pluteus.
• 3.3. The percentage of d-alanine with respect to the total alanine (d + l) decreases during embryonic development.
• 4.4. d-Amino acid oxidase, d-alanine transaminase and d-alanine racemase activities were found neither in eggs nor in embryos.
• 5.5. Therefore, it does not appear likely that d-alanine is subject to oxidative metabolism.
• 6.6. The decrease in this d-amino acid during development may be due to its utilization in the synthesis of a more complex molecule.

     

Enhanced Salt Tolerance of Rhizobia-inoculated Soybean Correlates with Decreased Phosphorylation of the Transcription Factor GmMYB183 and Altered Flavonoid Biosynthesis

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Highlights

• •Rhizobia affects flavonoid metabolism via GmMYB183 phosphorylation.
• •Flavonoids rebalance the cellular ROS under salt stress.
• •Mechanistic insights into soybean responses to salinity revealed by proteomics.

     

Evidence for extracellular deamination of adenosine in the rat heart

• 1.1. In rat heart perfused with adenosine (10⁻⁶M), dilazep (10⁻⁴M) inhibited incorporation of adenosine into nucleotides (an index of nucleoside transport and phosphorylation) to a greater extent (70%) than metabolism to inosine and uric acid (40%) and actually increased the recovery of inosine to 30% of the adenosine infused.
• 2.2. Extrapolating for complete inhibition of transport suggested that 60% of adenosine metabolism was intracellular and 40% extracellular.
• 3.3. Static incubations of atria also gave an estimate for extracellular metabolism of 40%.
• 4.4. Adenosine deaminase was localised by immunocytochemistry to the extracellular surface of endothelial cells of small coronary arteries.
• 5.5. Extracellular deamination may explain the lack of effect of nucleoside transport inhibitors on responses to adenosine in rat heart.

     

Analysis of the circadian rhythm in energy metabolism of rat liver

• 1.1. To study the temporal organization of energy metabolism in rat liver the steady state concentrations of key intermediates of carbohydrate and phosphorus metabolism were determined during 24 hr.
• 2.2. The circadian rhythm in energy metabolism of rat liver has been analysed by four different approaches. It was shown that neither apparent PEP synthesis nor crossover theorem were acceptable for the elucidation of the temporal organization of multi-enzyme systems.
• 3.3. Correlations analysis explained the temporal organization of energy metabolism most satisfactorily.
• 4.4. Based on the results of this analysis it was suggested that circadian regulation of energy metabolism in liver was realized at the level of the citric acid cycle.

     

Complement-like protein from the phylogenetically primitive vertebrate,Eptatretus Stouti,is a Humoral Opsonin

• 1.1. Serum from the Pacific hagfish,Eptatretus stouti,contains a complement-like protein (CLP).
• 2.2. CLP from unfractionated hagfish serum and from affinity-purified preparations binds to yeast cell surfaces.
• 3.3. Incubation with CLP enhances the phagocytosis of yeast by hagfish leukocytes.
• 4.4. CLP-mediated opsonization can be inhibited by anti-CLP antibody, EDTA, d(+)mannose and l(+)rhamnose.
• 5.5. Additional opsomic factors are also in hagfish serum.

     

Relationship between brain trehalase activity and trehalosema during direct and diapausing development in Pieris brassicae

• 1.1. Brain trehalase specific activity and trehalosemia were measured during the end of the developmental life cycle in non-diapausing and diapausing insects.
• 2.2. During non-diapausing development, trehalosemia reached maximum values at the beginning of pupal life. Then a constant decrease was observed up to the end of adult life.
• 3.3. The specific activity of brain trehalase was maximum when the insects were in active feeding periods, minimum activity appearing during moulting phases.
• 4.4. During diapausing development, trehalosemia was very high at the beginning of pupal life, particularly when insects were exposed to wintering conditions.
• 5.5. When diapause was broken, trehalosemia fell, announcing adult emergence.
• 6.6. Brain trehalase activity showed the same qualitative variations as in non-diapausing larvae, but with rather lower values.
• 7.7. During pupal life, brain trehalase activity decreased markedly during the long period necessary to obtain diapause breakdown.
• 8.8. Wintering conditions allow a progressive increase of brain trehalase activity, which preceded the fall of trehalosemia.

     

Bioelectric activity from isolated brain of Lacerta atlantica

• 1.1. A method of maintaining the isolated lizard brain in a Ringer solution is described.
• 2.2. Microelectrodes and EEG recordings from different areas of telecenphalon and optical tectum were made.
• 3.3. The prolonged cells survival under the experimental conditions described has been demonstrated for several hours.
• 4.4. The isolated brain of Lacerta makes it easy to reach anatomical pathways which otherwise, in the whole animal, would be more difficult to reach.

     

Interference of benzo[a]pyrene with cytochrome P-450-mediated steroid metabolism in pyloric caeca microsomes of the sea star Asterias rubens L.

• 1.1. The effects of benzo[a]pyrene (BaP) on the metabolism of progesterone and pregnenolone, and the effects of steroids on BaP metabolism were examined in pyloric caeca microsomes of female Asterias rubens.
• 2.2. The patterns of metabolism of progesterone and pregnenolone in microsomes were similar to those found in previous studies for homogenates and tissue incubations of pyloric caeca.
• 3.3. BaP reduced the rate of hydroxylation of progesterone and pregnenolone, but had no effect on metabolite formation by non-cytochrome P-450-catalysed reactions.
• 4.4. Microsomal BaP hydroxylase activity was reduced by the presence of progesterone, but pregnenolone and testosterone had no such effect.
• 5.5. The reductions in steroid or BaP metabolism were progressive with increasing ratios of the concentration of the interfering compound to that of the assay substrate and were maximally 50% or less at ratios of × 100.
• 6.6. It is concluded that isoenzymic forms of cytochrome P-450 are present, with preferences towards either steroid or BaP metabolism. The implications of the results for the in vivo situation are discussed.

     

Changes in high-energy phosphate metabolism in the water scorpion,Ranatra chinensis,under cold water-warm water stress

• 1.1. To evaluate changes in high-energy phosphate metabolism in the water scorpion (Ranatra chinensis) under restraint and cold water-warm water stresses, in vivo [³¹P]NMR spectra were obtained.
• 2.2. Under restraint stress, arginine phosphate (Arg-P) decreased by 10% after 1 hr and remained at that level thereafter, while β-ATP showed negligible changes over 6 hr.
• 3.3. As the water temperature gradually increased or decreased, the relative concentration of Arg-P decreased due to enzyme regulation.
• 4.4. Repeated cold water-warm water stress, which consisted of repeated 15 min exposures to cold water (5°C) followed by 15 min exposures to warm water (30°C) caused distinct decreases in Arg-P and β-ATP concentration. These decreases were dependent on the frequency of exposure.
• 5.5. Phosphomonoesters (PME) increased not only with restraint stress but also with cold water-warm water stress.
• 6.6. The effect of cold water-warm water stress on high-energy phosphate metabolism was greater than that of restraint stress.

     

Cholesterol metabolism in new world primates: Comparative studies in two tamarin species (Saguinus oedipus and Saguinus fuscicollis) and the squirrel monkey (Saimiri sciureus)

• 1.1. Cholesterol metabolism has been characterized in three species of New World primates, the cotton-top tamarin, the saddle-back tamarin, and the squirrel monkey.
• 2.2. When fed a diet containing cholesterol, the three species exhibited differing responses of plasma cholesterol levels.
• 3.3. Dietary cholesterol absorption was determined and plasma cholesterol die-away kinetics were analyzed in terms of a two-pool model.
• 4.4. The results of the analyses of cholesterol turnover are consistent with the observed species-specific differences in plasma cholesterol values and cholesterol absorption.
• 5.5. Cholesterol metabolism differs between the two tamarin species, as well as between the tamarins and the squirrel monkey.
• 6.6. Implications of species-specific differences between tamarin species are discussed in terms of the use of tamarin species as animal models for comparative studies of cholesterol metabolism and the etiology of cancer and cardiovascular disease.

     

Arginase,ornithine decarboxylase and S-adenosylmethionine decarboxylase in chicken brain and retina

• 1.1. Arginase, ornithine decarboxylase and S-adenosylmethionine decarboxylase are active in both retina and brain. Activity is higher in cerebellum than in the cerebral hemispheres and optical lobes.
• 2.2. Arginase and ornithine decarboxylase are very active in the retina of very young chicks, while S-adenosylmethionine decarboxylase is poorly active. By contrast, S-adenosylmethionine decarboxylase is much more active in brain.
• 3.3. The pattern of activity during development is different; only ornithine decarboxylase is very active during embryonal life; S-adenosylmethionine decarboxylase, at all events in brain, is more active in adult life.
• 4.4. Ornithine decarboxylase is inhibited in vitro by α-difluoromethylornithine, but not in vivo. Diaminopropane inhibits brain ornithine decarboxylase, but does not induce an ornithine decarboxylase-antizyme.
• 5.5. Methylglyoxal bis(guanylhydrazone) promotes an increase of S-adenosylmethionine decarboxylase activity in both the brain and the retina in vivo.

     

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Correlation of acid phosphatase but not alkaline phosphatase activity with myelination in the developing mouse brain

• 1.1. Neonatal mice received subcutaneous injections of buffer, thiourea (TU) or propylthiouracil (PTU).
• 2.2. The PTU-treated mice were sacrificed on postnatal day 14 (P14) and the TU-treated mice on P28.
• 3.3. Brain weights of the TU- and PTU-treated mice were not significantly different from the controls.
• 4.4. Acid but not alkaline phosphatase activity in the braistem decreased after TU and PTU treatment.
• 5.5. Myelination as indicated by intensity of luxol fast blue staining was weaker in drug-treated animals.
• 6.6. The level of myelin marker enzyme, 2′,3′-cyclic nucleotide 3′-phosphohydrolase, was lower in the brainstem of PTU-treated animals.
• 7.7. The results suggest a correlation between acid phosphatase but not alkaline phosphatase activity with myelination in the developing mouse brain.

     

A Platform for Extracellular Interactome Discovery Identifies Novel Functional Binding Partners for the Immune Receptors B7-H3/CD276 and PVR/CD155

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Highlights

• •New platform for high throughput detection of transient interactions between membrane proteins.
• •IL20RA is a receptor for the orphan checkpoint inhibitor B7-H3.
• •The natural killer cell protein KIR2DL5A binds the immune receptor PVR.
• •KIR2DL5 binding to PVR regulates natural killer cell cytotoxicity and inhibits tumor cell killing.
• •Elucidation of receptor interactomes to gain insights into extracellular protein biology.

     

BioID Performed on Golgi Enriched Fractions Identify C10orf76 as a GBF1 Binding Protein Essential for Golgi Maintenance and Secretion

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Highlights

• •BioID with Golgi fractions identified C10orf76 as proximal to GBF1.
• •Tagged C10orf76 overlaps with Golgi markers.
• •C10orf76 binds GBF1 and exchanges rapidly between free and bound forms.
• •C10orf76 is essential for maintenance of the Golgi and for secretion.

     

Anaerobic threshold in rats

• 1.1. The aim of this study was to find out whether the anaerobic threshold (AT) can be estimated in rats running at increasing speed and if so what is the reproducibility of the measurements.
• 2.2. Lactate (LA) concentrations in blood taken from 11 rats were determined during a discontinued, multistage treadmill exercise test repeated four times in each animal.
• 3.3. It was found that blood LA changes vs speed have an exponential pattern with a distinct, rapid rise at the speed above 25 m/min which corresponds to blood LA of approx. 4 mmol/1.
• 4.4. The variation coefficient of the speed at which AT occurred in individual animals ranged between 10 and 20%.
• 5.5. These results offer a potential application of AT determination in the animal studies concerning mechanisms controlling exercise metabolism.

     

Quantitative Proteomics Links the Intermediate Filament Nestin to Resistance to Targeted BRAF Inhibition in Melanoma Cells

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Highlights

• •Quantitative phosphoproteome of BRAF drug-resistance in melanoma cells.
• •Cytoskeletal proteins are downregulated in resistant vs. sensitive cells.
• •Nestin is associated with an invasive phenotype and resistance to MEK and BRAF inhibitors.
• •Nestin depletion affects PI3K/AKT and integrin signaling similar to resistant cells.