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Biomedical subjects

L Hue

Publications and source records attributed to L Hue.

At least 91 records · Page 5Linked to original sources
PubMed1989

Effects of alinidine on metabolic response to high-demand myocardial ischemia.

Alinidine is a new bradycardic agent that interferes with ion channels and the if pacemaker current. To determine if alinidine had antiischemic effects unrelated to its bradycardic action, myocardial metabolism was studied during a pacing-stress test in 20 patients with coronary artery disease and angina pectoris, before and after intravenous infusion of alinidine (10 mg, n = 10; 50 mg, n = 10). When compared to the control pacing-stress test, the low dose of alinidine had no significant effect on aortic pressure, coronary sinus flow (-3%, NS), myocardial oxygen extraction, or myocardial lactate uptake. After the high dose of alinidine, aortic pressure and coronary sinus flow remained unchanged but the arteriocoronary sinus difference in oxygen content increased (12.2 +/- 1.3 to 12.7 +/- 1.4 ml/100 ml; p less than 0.0002) above the values observed during the control pacing-stress test, while both the chemical lactate extraction fraction (-19 +/- 30 to 15 +/- 21%; p less than 0.025) and the L-[1-14C]lactate extraction fraction increased. Accordingly, the net myocardial lactate uptake (corrected for production) had increased from 14 +/- 32 during the control pacing-stress test to 29 +/- 24 mumol/min during the pacing repeated after the high dose of alinidine (p less than 0.05). After the high dose of alinidine, the free fatty acid uptake also rose slightly (+23%; NS) and the alanine production was reduced in 7 of 10 patients (-3.6 +/- 1.7 to -1.4 +/- 0.6 mumol/min; NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

[Fructose-2,6-diphosphate and glycolysis of tumor cells].

Tumour and proliferative cells maintain a high glycolytic rate even under aerobic conditions. The discovery of fructose-2,6-bisphosphate, a potent stimulator of glycolysis, has prompted a re-investigation of this phenomenon. Rat hepatoma cells and fibroblasts stimulated by mitogens or transformed by the Rous sarcoma virus, were used as models. The results indicate that the stimulation of glycolysis induced by these agents can be explained by an increase in the concentration of fructose-2,6-bisphosphate and in the activity of the enzyme synthesizing it.

Animals↗
PubMed1988

Fructose 2,6-bisphosphate and its phosphorothioate analogue. Comparison of their hydrolysis and action on glycolytic and gluconeogenic enzymes.

Purified chicken liver 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase was phosphorylated either from fructose 2,6-bis[2-32P]phosphate or fructose 2-phosphoro[35S]thioate 6-phosphate. The turnover of the thiophosphorylated enzyme intermediate as well as the overall phosphatase reaction was four times faster than with authentic fructose 2,6-bisphosphate. Fructose 2-phosphorothioate 6-phosphate was 10-100-fold less potent than authentic fructose 2,6-bisphosphate in stimulating 6-phosphofructo-1-kinase and pyrophosphate:fructose 6-phosphate phosphotransferase, but about 10 times more potent in inhibiting fructose 1,6-bisphosphatase. The analogue was twice as effective as authentic fructose 2,6-bisphosphate in stimulating pyruvate kinase from trypanosomes.

Animals↗
PubMed1988

Rat hepatoma (HTC) cell 6-phosphofructo-2-kinase differs from that in liver and can be separated from fructose-2,6-bisphosphatase.

6-Phosphofructo-2-kinase was purified from rat liver and hepatoma (HTC) cells. The HTC cell enzyme had kinetic properties different from those of the liver enzyme (more sensitive to inhibition by citrate and not inhibited by sn-glycerol 3-phosphate) and was not a substrate of the cyclic-AMP-dependent protein kinase. Unlike the liver enzyme, which is bifunctional and phosphorylated by fructose 2,6-[2-32P]bisphosphate, the HTC cell enzyme contained no detectable fructose-2,6-bisphosphatase activity and phosphorylation by fructose 2,6-[2-32P]-bisphosphate could not be detected. HTC cell fructose-2,6-bisphosphatase could be separated from 6-phosphofructo-2-kinase activity by purification. Antibodies raised against liver 6-phosphofructo-2-kinase did not precipitate HTC cell fructose-2,6-bisphosphatase whose kinetic properties were completely different from those of the liver enzyme.

Animals↗
PubMed1988

Changes in coronary blood flow and myocardial metabolism during aortic balloon valvuloplasty.

The effects of balloon inflation on myocardial perfusion and metabolism were studied during aortic valvuloplasty in 17 patients with aortic stenosis, including 6 with associated coronary artery disease. Coronary sinus flow and blood samples were obtained before and during the first inflation, and 5 to 10 minutes after the last inflation. During inflation, coronary blood flow decreased (272 +/- 111 standard deviation to 166 +/- 92 ml/min; p less than 0.05), myocardial oxygen uptake fell and transcardiac lactate handling shifted from extraction to production (35 +/- 54 to -41 +/- 48 mumol/min; p less than 0.01). At the end of the procedure, aortic valve area had increased from 0.51 +/- 0.22 to 0.81 +/- 0.48 cm2 (p less than 0.002). Coronary sinus flow increased slightly above control values (+6%; difference not significant) and myocardial oxygen and lactate uptakes were back to control values. However, myocardial alanine production had increased from -3.6 to -6.6 mumol/min (p less than 0.05) and glutamine production was reduced or replaced by extraction (-3.3 +/- 2.1 to 3.5 +/- 3.8 mumol/min; p less than 0.05). Recovery of coronary flow, oxygen and lactate uptakes was not significantly different in patients with or without coronary artery disease, although the former patients tended to have less glutamine extraction and less improvement in their ejection fraction at the end of the procedure. Thus, aortic balloon valvuloplasty produces brief episodes of low-flow ischemia. Recovery of oxidative metabolism is almost immediate after deflation and no detrimental effect seems to persist at the end of the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Palmitate inhibits liver glycolysis. Involvement of fructose 2,6-bisphosphate in the glucose/fatty acid cycle.

In hepatocytes from overnight-fasted rats incubated with glucose, palmitate decreased the production of lactate, the detritiation of [2-3H]- and [3-3H]-glucose, and the concentration of fructose 2,6-bisphosphate. Similarly, perfusion of hearts from fed rats with beta-hydroxybutyrate resulted in an inhibition of the detritiation of [3-3H]glucose and a fall in fructose 2,6-bisphosphate concentration. This fall could result from an increase in citrate (hepatocytes and heart) and sn-glycerol 3-bisphosphate concentration. It is suggested that a fall in fructose 2,6-bisphosphate concentration participates in the inhibition of glycolysis by fatty acids and ketone bodies.

3-Hydroxybutyric Acid↗
PubMed1988

Starvation or diabetes decreases the content but not the mRNA of 6-phosphofructo-2-kinase in rat liver.

In rat liver, the activity of 6-phosphofructo-2-kinase (PFK-2) decreases upon starvation and in diabetes. Cyclic AMP-dependent phosphorylation of the enzyme is not sufficient to account for this decrease. PFK-2 content was therefore measured by immunotitration and relative PFK-2 mRNA levels were determined by hybridization with cDNA probes. The data are compatible with a posttranscriptional mechanism of regulation that involves decreased translational efficiency of PFK-2 mRNA and (or) increased turnover of the PFK-2 protein.

Animals↗
PubMed1988

Effects of intracoronary infusion of nicardipine during silent ischaemia on myocardial metabolism and function.

The effects of an intracoronary infusion of nicardipine (0.2 mg over 10 min) on myocardial substrate uptake and function were studied in 16 patients with coronary artery disease and angina pectoris. Silent ischaemia, demonstrated by myocardial lactate production, was induced twice by pacing below anginal threshold. Nicardipine or saline was randomly infused during the first or second pacing. During pacing with nicardipine, no systemic effect was noted but coronary sinus flow increased (+ 18%; P less than 0.015) and myocardial oxygen uptake decreased by 12% (P less than 0.025). Transcardiac lactate production did not improve (-8 to -10 mumol min-1; NS) but net lactate uptake, estimated from radiolabelled lactate uptake, tended to rise and the glutamine uptake increased from 1.8 to 5.5 mumol min-1 (P less than 0.04). During recovery after pacing, lactate production decreased faster and LV peak (+) dP/dt and relaxation rate were significantly better after nicardipine infusion than after saline. Thus, during silent ischaemia induced by an increased oxygen demand, intracoronary nicardipine did not prevent lactate release but allowed a faster metabolic and functional recovery. These beneficial effects of nicardipine could be explained by an improved myocardial perfusion or by an effect on intracellular calcium homeostasis.

Adult↗
PubMed1987

Stimulation of glycogen synthesis and lipogenesis by glutamine in isolated rat hepatocytes.

Glutamine stimulated glycogen synthesis and lactate production in hepatocytes from overnight-fasted normal and diabetic rats. The effect, which was half-maximal with about 3 mM-glutamine, depended on glucose concentration and was maximal below 10 mM-glucose. beta-2-Aminobicyclo[2.2.1.]heptane-2-carboxylic acid, an analogue of leucine, stimulated glutaminase flux, but inhibited the stimulation of glycogen synthesis by glutamine. Various purine analogues and inhibitors of purine synthesis were found to inhibit glycogen synthesis from glucose, but they did not abolish the stimulatory effect of glutamine on glycogen synthesis. The correlation between the rate of glycogen synthesis and synthase activity suggested that the stimulation of glycogen synthesis by glutamine depended solely on the activation of glycogen synthase. This activation of synthase was not due to a change in total synthase, nor was it caused by a faster inactivation of glycogen phosphorylase, as was the case after glucose. It could, however, result from a stimulation of synthase phosphatase, since, after the addition of 1 nM-glucagon or 10 nM-vasopressin, glutamine did not interfere with the inactivation of synthase, but did promote its subsequent re-activation. Glutamine was also found to inhibit ketone-body production and to stimulate lipogenesis.

Animals↗
PubMed1987

Extracellular metabolites in suspensions of isolated hepatocytes.

The activity of lactate dehydrogenase and the concentration of several metabolites were measured in a suspension of isolated hepatocytes and in the extracellular medium, obtained after elimination of the cells by centrifugation for 15 s. The initial proportions of ATP, fructose 2,6-bisphosphate and glycogen present in the medium were similar to that of lactate dehydrogenase, and were therefore explained by unavoidable cell breakage occurring during resuspension of the hepatocytes. ATP disappeared from the medium in less than 10 min, being presumably destroyed by membrane nucleotidases. By contrast, the proportions of hexose 6-phosphates and of glycerol 3-phosphate in the medium were several-fold in excess over that of lactate dehydrogenase; under certain conditions, the extracellular value accounted for 80-90% of the metabolite present in the total suspension, and there was no relationship between the extra- and intracellular concentrations of these metabolites. A potential source of external glycerol 3-phosphate was the hydrolysis of glycerophosphocholine by membranous enzymes. The main conclusion of this work is that the measurement, in isolated hepatocytes, of hexose 6-phosphates, glycerol 3-phosphate and possibly other metabolites that were not investigated, requires the previous separation of the cells from the incubation medium. This conclusion may apply to other cellular suspensions.

Adenosine Triphosphate↗
PubMed1987

Complete nucleotide sequence coding for rat liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase derived from a cDNA clone.

cDNA clones for 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase were isolated from rat liver expression libraries in lambda gt11 by antibody, oligonucleotide, and cDNA screening. One 1860 bp long clone contained a full-length nucleotide sequence coding for the 470 amino acids of each of the two identical subunits of the bifunctional enzyme. This clone also contained untranslated sequences, one 173 bp long upstream from the ATG start codon and one 271 bp long downstream from the TGA stop codon. The clone was terminated by a poly(A) tail of 29 nucleotides.

Amino Acid Sequence↗
PubMed1987

Fructose 2,6-bisphosphate in rat erythrocytes. Inhibition of fructose 2,6-bisphosphate synthesis and measurement by glycerate 2,3-bisphosphate.

The concentration of fructose 2,6-bisphosphate found in freshly isolated erythrocytes was below the limit of detection (20 pmol/ml of packed cells). However, it increased to about 250 pmol/ml of cells when erythrocytes were incubated with glucose at pH 6.9, but not at pH 7.4 or 8.2. This could be explained by variations in the content of glycerate 2,3-bisphosphate, which was found to inhibit 6-phosphofructo-2-kinase, the enzyme responsible for fructose 2,6-bisphosphate synthesis. Glycerate 2,3-bisphosphate was also found to inhibit the potato enzyme (pyrophosphate:fructose-6-phosphate 1-phosphotransferase) used for the measurement of fructose 2,6-bisphosphate.

2,3-Diphosphoglycerate↗
PubMed1986

Inhibition of gluconeogenesis by hypoglycin in the rat. Evidence for inhibition of glucose-6-phosphatase in vivo.

Treatment of rats with hypoglycaemic doses of hypoglycin has been shown to abolish the relative detritiation of [2-3H,U-14C]glucose [Osmundsen, Billington, Taylor & Sherratt (1978) Biochem. J. 170, 337-342], indicating that both the Cori and the glucose/glucose 6-phosphate cycles were inhibited in vivo. This inhibition was confirmed and, in addition, it was shown that the conversion in vivo of both [14C]lactate and [14C]fructose into glucose was decreased after hypoglycin treatment. These results suggest that hypoglycin poisoning results in the inhibition in vivo of glucose-6-phosphatase activity, which participates in the overall inhibition of gluconeogenesis and hypoglycaemia. Clofibrate feeding apparently protected the rats against the inhibition of the fructose-to-glucose conversion by hypoglycin. However, in isolated hepatocytes prepared from hypoglycin-treated rats, the conversion of [14C]fructose into glucose and the recycling of [2-3H,U-14C]glucose were not different from that in control hepatocytes. This suggests that the inhibition was lost during preparation of the hepatocytes. The direct measurement of glucose-6-phosphatase activity showed that it was inhibited when measured in concentrated, but not dilute, homogenates prepared from hypoglycin-treated rats.

Animals↗
PubMed1986

Phosphorylation of purified bovine heart and rat liver 6-phosphofructo-2-kinase by protein kinase C and comparison of the fructose-2,6-bisphosphatase activity of the two enzymes.

Purified bovine heart 6-phosphofructo-2-kinase can be phosphorylated in the presence of protein kinase C and dephosphorylated by alkaline phosphatase; changes in phosphorylation state have no effect on enzyme activity. By contrast, the rat liver enzyme is a poor substrate for protein kinase C. Unlike the liver enzyme, which is bifunctional and is phosphorylated by fructose 2,6-[2-32P]bisphosphate, the heart enzyme contains 10 times less fructose 2,6-bisphosphatase activity and is phosphorylated at a slower rate and to a lesser extent than the liver enzyme. Both rat liver and bovine heart enzymes catalyse a similar exchange reaction between [U-14C]ADP and ATP.

Animals↗
PubMed1986

Expression of the v-src or v-fps oncogene increases fructose 2,6-bisphosphate in chick-embryo fibroblasts. Novel mechanism for the stimulation of glycolysis by retroviruses.

The concentration of fructose 2,6-bisphosphate and the activity of 6-phosphofructo-2-kinase are increased after infection of chick-embryo fibroblasts with the Rous sarcoma virus, or with a temperature-sensitive mutant of this virus at the permissive, but not at the non-permissive, temperature. This is observed after transformation by retroviruses carrying either the v-src or v-fps, but not the v-mil and/or v-myc, oncogenes. Comparison of the effects of the Rous sarcoma virus with those of phorbol myristate acetate on fructose 2,6-bisphosphate suggests that both result from the stimulation of a step which is rate-limiting for 6-phosphofructo-2-kinase activation and which is also controlled by protein kinase C.

Animals↗
PubMed1986

Fructose 2,6-bisphosphate and the control of glycolysis in bovine spermatozoa.

Epididymal bovine sperm contain fructose-1,6-bisphosphatase activity which is inhibited by AMP and by fructose 2,6-bisphosphate. Sperm phosphofructokinase displays kinetic characteristics that are typical of the F-type and it is stimulated by fructose 2,6-bisphosphate. The concentration of sperm fructose 2,6-bisphosphate remained unaffected at 1-2 microM when the glycolytic rate was either increased by glucose, caffeine or antimycin, or decreased by alpha-chlorohydrin or 6-chloro-6-deoxyglucose.

Animals↗