scholarly journals The effects of the exogenous provision of lactate and the endogenous production of lactate on protein synthesis in the heart

1992 ◽  
Vol 281 (1) ◽  
pp. 121-127 ◽  
Author(s):  
S J Fuller ◽  
P H Sugden
Keyword(s):  
Protein Synthesis ◽  
Adenine Nucleotides ◽  
Lactate Concentration ◽  
Lactate Production ◽  
Endogenous Production ◽  
Maximal Stimulation ◽  
Exogenous Addition ◽  
Lactate Uptake ◽  
Best Fit ◽  
Stimulation Of

We have investigated the effects of exogenous addition of lactate and of the stimulation of endogenous production of lactate on protein synthesis in the anterogradely perfused rat heart. In the absence of exogenous lactate, hearts release lactate into the perfusate. At lactate concentrations of 0.2 mM and greater, the heart takes up lactate. The best fit for lactate uptake plotted against exogenous lactate concentration is a rectangular hyperbola with a maximal rate of 220 mumol/2 h per heart (wet wt. about 1 g). Uptake is half-maximal at about 1.3 mM-lactate. The stimulation of protein synthesis also exhibits a rectangular-hyperbolic dependence on exogenous lactate concentration, with maximal stimulation being about 38%. Half-maximal stimulation occurs at about 0.9 mM-lactate. We stimulated endogenous lactate production by perfusion with 2-cyanocinnamate (an inhibitor of mitochondrial pyruvate transport) at concentrations up to 70 microM. Cardiac outputs, intracellular pH and the concentrations of phosphocreatine and the adenine nucleotides were not altered. Atrial protein-synthesis rates were unchanged, but ventricular rates were decreased. We conclude that endogenous lactate production is unlikely to stimulate protein synthesis and that the stimulation of protein synthesis by exogenous lactate is related to its uptake.

Insulin action in pancreatic acini from streptozotocin-treated rats. II. Binding of 125I-insulin to receptors

1981 ◽  
Vol 240 (1) ◽  
pp. G63-G68 ◽  
Author(s):  
H. Sankaran ◽  
Y. Iwamoto ◽  
M. Korc ◽  
J. A. Williams ◽  
I. D. Goldfine
Keyword(s):  
Protein Synthesis ◽  
Binding Sites ◽  
Insulin Binding ◽  
Diabetic Rats ◽  
Cell Protein ◽  
Scatchard Analysis ◽  
Pancreatic Acini ◽  
Maximal Stimulation ◽  
Major Class ◽  
Stimulation Of

The binding of 125I-insulin to its receptors was investigated with isolated pancreatic acini obtained from diabetic rats under incubation conditions identical to those used to study the effects of insulin on acinar cell protein synthesis. Binding was specific, time dependent, reversible, and linearly related to the acinar protein content. Degradation of insulin after 30 min of incubation was less than 10% of the total hormone present in the incubation medium. 125I-insulin dissociated from acini with a one-half time of 9 min. Unlabeled insulin at 83.5 nM accelerated the rate of dissociation of labeled insulin. 125I-insulin binding to acini was competitively inhibited by insulin and its analogues in proportion to their biological potencies. Scatchard analysis revealed a major class of insulin-binding sites with a Kd of 1.6 nM; maximal stimulation of protein synthesis was observed when > 90% of these high-affinity receptors were occupied. These studies indicate, therefore, that insulin binding to receptors on pancreatic acini can be correlated with subsequent regulation of biological functions.

Protein synthesis is activated in primed neutrophils: a possible role in inflammation

1987 ◽  
Vol 7 (11) ◽  
pp. 881-890 ◽  
Author(s):  
Valerie Hughes ◽  
John M. Humphreys ◽  
Steven W. Edwards
Keyword(s):  
Protein Synthesis ◽  
Actinomycin D ◽  
Protein Biosynthesis ◽  
Polyacrylamide Gel Electrophoresis ◽  
Human Neutrophils ◽  
Chemotactic Peptide ◽  
Inflammatory Agent ◽  
Maximal Stimulation ◽  
Stimulation Of ◽  
Primed Neutrophil

Circulating human neutrophils exhibited low rates of protein biosynthesis, as determined by their ability to incorporate [35S]methionine into TCA-precipitable material. Exposure of cells to the chemotactic peptide (N-formyl-L-methionyl-L-leucyl-L-phenylalanine) increased their rate of protein synthesis, and the maximal stimulation of biosynthesis by this inflammatory agent was observed at 0.1 μM: this concentration of chemotactic peptide “primed” neutrophil activity and only activated the oxidase of these cells by 8% of maximum. The newly-synthesized proteins were analyzed by two-dimensional polyacrylamide gel electrophoresis and compared with those synthesized in control cells. Two classes of proteins were observed in “primed” cells. The first of these comprised proteins whose rate of biosynthesis changed very little upon “priming” whereas the second class comprised proteins whose rate of synthesis increased greatly after exposure to chemotactic peptide. The fMet-Leu-Phe stimulated protein synthesis was inhibited by actinomycin D and cycloheximide showing that this phenomenon required both transcription and translation. We propose that these fMet-Leu-Phe regulated proteins play an important role in the function of neutrophils during an inflammatory response.

scholarly journals Role of fructose 2,6-bisphosphate in the stimulation of glycolysis by anoxia in isolated hepatocytes

1982 ◽  
Vol 206 (2) ◽  
pp. 359-365 ◽  
Author(s):  
L Hue
Keyword(s):  
Skeletal Muscle ◽  
Cyclic Amp ◽  
Adenine Nucleotides ◽  
Lactate Production ◽  
Isolated Hepatocytes ◽  
Anaerobic Glycolysis ◽  
Anaerobic Conditions ◽  
Effect Of Glucose ◽  
Stimulation Of

1. Incubation of hepatocytes from fed or starved rats with increasing glucose concentrations caused a stimulation of lactate production, which was further increased under anaerobic conditions. 2. When glycolysis was stimulated by anoxia, [fructose 2,6-bis-phosphate] was decreased, indicating that this ester could not be responsible for the onset of anaerobic glycolysis. In addition, the effect of glucose in increasing [fructose 2,6-bisphosphate] under aerobic conditions was greatly impaired in anoxic hepatocytes. [Fructose 2,6-bisphosphate] was also diminished in ischaemic liver, skeletal muscle and heart. 3. The following changes in metabolite concentration were observed in anaerobic hepatocytes: AMP, ADP, lactate and L-glycerol 3-phosphate were increased; ATP, citrate and pyruvate were decreased: phosphoenolpyruvate and hexose 6-phosphates were little affected. Concentrations of adenine nucleotides were, however, little changed by anoxia when hepatocytes from fed rats were incubated with 50 mM-glucose. 4. The activity of ATP:fructose 6-phosphate 2-phosphotransferase was not affected by anoxia but decreased by cyclic AMP. 5. The role of fructose 2,6-bisphosphate in the regulation of glycolysis is discussed.

Regulation of lactate uptake and lactate production in liver from 48-h-starved rats: Effects of pH, flow and glucose concentration

1988 ◽  
Vol 74 (4) ◽  
pp. 403-406 ◽  
Author(s):  
Leif Sestoft ◽  
Michael O. Marshall
Keyword(s):  
Glucose Concentration ◽  
Lactate Concentration ◽  
Lactate Production ◽  
Low Ph ◽  
Low Flow ◽  
Normal Flow ◽  
Ph Values ◽  
Effects Of Ph ◽  
Inhibition Of Glycolysis ◽  
Lactate Uptake

1. The effects of medium glucose concentration (0–20 mmol/l) and flow (100–33% of normal) on lactate uptake at low lactate concentration were studied in perfused livers from 48-h-starved rats with perfusate pH values of 7.4 and 6.8. 2. Lactate uptake was independent of glucose concentration in the range 5–10 mmol/l, but was slightly inhibited with time at 20 mmol/l glucose. This pattern was independent of perfusate pH. 3. At both pH values lactate uptake decreased proportionally with flow, and at low flow lactate was produced by the livers. The effect of flow was greatest at pH 7.4 where a net lactate production was found at 48% of normal flow, whereas at pH 6.8 lactate production was not seen until the flow was reduced to 33% of normal. 4. When glucose was omitted from the perfusate lactate production ceased at both pH values. 5. The effect of low pH on lactate uptake and production in liver probably reflects inhibition of glycolysis by low pH.

Acceleration of growth of cultured cardiomyocytes and translocation of protein kinase C

1992 ◽  
Vol 263 (2) ◽  
pp. C319-C325 ◽  
Author(s):  
S. N. Allo ◽  
L. L. Carl ◽  
H. E. Morgan
Keyword(s):  
Protein Synthesis ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Time Course ◽  
Growth Stimulation ◽  
Primary Role ◽  
Kinase C ◽  
Maximal Stimulation ◽  
Rna Content ◽  
Stimulation Of

Phorbol 12-myristate 13-acetate (PMA), norepinephrine (NE), and contraction stimulate cardiomyocyte growth (increased protein content). Differences exist in the time course and extent of protein and RNA accumulation. Cells plated at 4 x 10(6) cells/60-mm dish and arrested with 50 mM KCl demonstrated no significant growth. Treatment with PMA stimulated growth to a maximum of 17% at 48 h. In contrast, maximal stimulation of growth was 36% at 48 h and 31% at 72 h for contracting and NE-treated cells, respectively. Maximal stimulation of the capacity for protein synthesis (RNA content) was 32% for PMA-treated cells at 24 h compared with 59% and 77% for NE-treated and contracting cells, respectively, at 72 h. In support of a primary role for altered capacity in the regulation of protein synthesis, there was a significant correlation (r = 0.84) between RNA and protein contents that was independent of the stimulus used. Angiotensin II increased RNA content by 28% at 48 h but had no effect on growth up to 72 h. Growth stimulation and increased nuclear protein kinase C (PKC) activity were induced by contraction, NE, and PMA treatment and were inhibited by staurosporine (a PKC inhibitor), suggestive of a central role for PKC.

Hormonal control of protein synthesis in chick chondrocytes: a comparison of effects of insulin, somatomedin C and triiodothyronine

1984 ◽  
Vol 107 (2) ◽  
pp. 179-184 ◽  
Author(s):  
Stephen F. Kemp ◽  
Murry Mutchnick ◽  
Raymond L. Hintz
Keyword(s):  
Protein Synthesis ◽  
Actinomycin D ◽  
Specific Binding ◽  
Hormonal Control ◽  
Somatomedin C ◽  
Maximal Stimulation ◽  
Fold Stimulation ◽  
Translational Process ◽  
Stimulation Of

Abstract. Somatomedin C (SM-C), insulin, and triiodothyronine (T3) each result in a 2-fold stimulation of incorporation of [125I]leucine into protein by cultured chick sternal chondrocytes. Maximal stimulation occurred at concentrations of 12.5 × 10−9 m SM-C, 11 × 10−9 m insulin, and 1.5 × 10−9 m T3. Submaximal concentrations of SM-C and T3 were additive in their effect, and together stimulated [125I]leucine incorporated to a level greater than that achieved by either alone. Submaximal concentrations of SM-C and insulin were also additive in their stimulatory effect, but only to the level achieved by either alone. It was possible to demonstrate specific binding of [14C]SM-C to chondrocytes, and bound SM-C could be displaced by either unlabelled SM-C or insulin at concentrations similar to concentrations that stimulated protein synthesis. Actinomycin D abolished stimulation by T3, but not by insulin or SM-C. Thus, it appears that SM-C and insulin increase protein synthesis by stimlating the translational process after binding to the same receptor. T3 appears to act through a different mechanism, which requires stimulation of transcription.

scholarly journals Stimulation of glycogenolysis by adenine nucleotides in the perfused rat liver

1986 ◽  
Vol 237 (3) ◽  
pp. 773-780 ◽  
Author(s):  
D B Buxton ◽  
S M Robertson ◽  
M S Olson
Keyword(s):  
Cyclic Amp ◽  
Adenine Nucleotides ◽  
Hepatic Metabolism ◽  
Hepatic Tissue ◽  
Adrenergic Stimulation ◽  
Portal Vein Pressure ◽  
Maximal Stimulation ◽  
Phenylephrine Infusion ◽  
Glucose Output ◽  
Stimulation Of

Infusion of adenine nucleotides and adenosine into perfused rat livers resulted in stimulation of hepatic glycogenolysis, transient increases in the effluent perfusate [3-hydroxybutyrate]/[acetoacetate] ratio, and increased portal vein pressure. In livers perfused with buffer containing 50 microM-Ca2+, transient efflux of Ca2+ was seen on stimulation of the liver with adenine nucleotides or adenosine. ADP was the most potent of the nucleotides, stimulating glucose output at concentrations as low as 0.15 microM, with half-maximal stimulation at approx. 1 microM, and ATP was slightly less potent, half-maximal stimulation requiring 4 microM-ATP. AMP and adenosine were much less effective, doses giving half-maximal stimulation being 40 and 20 microM respectively. Non-hydrolysed ATP analogues were much less effective than ATP in promoting changes in hepatic metabolism. ITP, GTP and GDP caused similar changes in hepatic metabolism to ATP, but were 10-20 times less potent than ATP. In livers perfused at low (7 microM) Ca2+, infusion of phenylephrine before ATP desensitized hepatic responses to ATP. Repeated infusions of ATP in such low-Ca2+-perfused livers caused homologous desensitization of ATP responses, and also desensitized subsequent Ca2+-dependent responses to phenylephrine. A short infusion of Ca2+ (1.25 mM) after phenylephrine infusion restored subsequent responses to ATP, indicating that, during perfusion with buffer containing 7 microM-Ca2+, ATP and phenylephrine deplete the same pool of intracellular Ca2+, which can be rapidly replenished in the presence of extracellular Ca2+. Measurement of cyclic AMP in freeze-clamped liver tissue demonstrated that adenosine (150 microM) significantly increased hepatic cyclic AMP, whereas ATP (15 microM) was without effect. It is concluded that ATP and ADP stimulate hepatic glycogenolysis via P2-purinergic receptors, through a Ca2+-dependent mechanism similar to that in alpha-adrenergic stimulation of hepatic tissue. However, adenosine stimulates glycogenolysis via P1-purinoreceptors and/or uptake into the cell, at least partially through a mechanism involving increase in cyclic AMP. Further, the hepatic response to adenine nucleotides may be significant in regulating hepatic glucose output in physiological and pathophysiological states.

Active muscle and whole body lactate kinetics after endurance training in men

1999 ◽  
Vol 87 (5) ◽  
pp. 1684-1696 ◽  
Author(s):  
Bryan C. Bergman ◽  
Eugene E. Wolfel ◽  
Gail E. Butterfield ◽  
Gary D. Lopaschuk ◽  
Gretchen A. Casazza ◽  
...  
Keyword(s):  
Endurance Training ◽  
Power Output ◽  
Lactate Concentration ◽  
Lactate Production ◽  
Lactate Clearance ◽  
Cycle Ergometer ◽  
Whole Body ◽  
Moderate Intensity ◽  
Metabolic Clearance ◽  
Lactate Uptake

We evaluated the hypotheses that endurance training decreases arterial lactate concentration ([lactate]a) during continuous exercise by decreasing net lactate release (L˙) and appearance rates (Ra) and increasing metabolic clearance rate (MCR). Measurements were made at two intensities before [45 and 65% peak O2consumption (V˙o 2 peak)] and after training [65% pretrainingV˙o 2 peak, same absolute workload (ABT), and 65% posttrainingV˙o 2 peak, same relative intensity (RLT)]. Nine men (27.4 ± 2.0 yr) trained for 9 wk on a cycle ergometer, 5 times/wk at 75%V˙o 2 peak. Compared with the 65%V˙o 2 peakpretraining condition (4.75 ± 0.4 mM), [lactate]a decreased at ABT (41%) and RLT (21%) ( P < 0.05). L˙ decreased at ABT but not at RLT. Leg lactate uptake and oxidation were unchanged at ABT but increased at RLT. MCR was unchanged at ABT but increased at RLT. We conclude that 1) active skeletal muscle is not solely responsible for elevated [lactate]a; and 2) training increases leg lactate clearance, decreases whole body and leg lactate production at a given moderate-intensity power output, and increases both whole body and leg lactate clearance at a high relative power output.

scholarly journals Stimulation of cardiac protein synthesis by insulin-like growth factors

1992 ◽  
Vol 282 (1) ◽  
pp. 85-90 ◽  
Author(s):  
S J Fuller ◽  
J R Mynett ◽  
P H Sugden
Keyword(s):  
Protein Synthesis ◽  
Growth Factors ◽  
Growth Factor ◽  
Lactate Production ◽  
Adult Rats ◽  
Mechanistic Basis ◽  
High Concentrations ◽  
Stimulation Of ◽  
Insulin Like Growth Factors

The effects of the insulin-like growth factors (IGF)-1 and -2 on the rates of protein synthesis in freshly isolated cardiac myocytes from adult rats were compared with those of insulin. At concentrations of 50-100 nM, each agent stimulated protein synthesis by about 70%. There was no additional stimulation upon combination of insulin with IGF-1 or IGF-2 at these high concentrations. When compared over a range of concentrations, the relative response to each agent was insulin greater than IGF-1 greater than or equal to IGF-2. Concentrations of 1 nM-IGF-1, 1 nM-IGF-2 or 0.2 nM-insulin enhanced the rates of protein synthesis by 36%, 30% or 34% respectively. A combination of 0.2 nM-insulin and 1 nM-IGF-1 or 1 nM-IGF-2 increased the stimulation of protein synthesis to 46%. In contrast, the effects of 1 nM-IGF-1 and 1 nM-IGF-2 were not additive. The possible mechanistic basis for this difference is discussed. At a concentration of 50 nM, epidermal growth factor (EGF), fibroblast growth factor and platelet-derived growth factor were each without effect on protein synthesis. In anterogradely perfused rat heart preparations, 2 nM-IGF-1 or 2.4 nM-IGF-2 increased protein synthesis and lactate production, but 9.2 nM-EGF did not. From a consideration of the plasma free concentrations of IGF-1 and IGF-2, we suggest that these factors may contribute to the maintenance of rate of cardiac protein synthesis in vivo.

EFFECT OF ACTINOMYCIN D ON TSH-INDUCED STIMULATION OF THYROIDAL PROTEIN SYNTHESIS IN THE RAT

1974 ◽  
Vol 77 (1) ◽  
pp. 64-70 ◽  
Author(s):  
Gustav Wägar
Keyword(s):  
Protein Synthesis ◽  
Actinomycin D ◽  
The Other ◽  
Leucine Incorporation ◽  
Short Term ◽  
Other Hand ◽  
Thyroid Glands ◽  
Translational Level ◽  
Stimulation Of

ABSTRACT Whether the short-term regulation of thyroidal protein synthesis by TSH occurs at the transcriptional or the translational level was tested by measuring the effect of actinomycin D (act D) on the TSH-induced stimulation of L-14C-leucine incorporation into the thyroidal proteins of rats. TSH was injected 6 h before the rats were killed. The thyroid glands were then removed and incubated in vitro in the presence of L-14C-leucine for 2 h. The pronounced stimulation of leucine incorporation in the TSH-treated animals was depressed as compared with controls but still significant even when the animals had been pre-treated with 100 μg act D 24 and 7 h before sacrifice. On the other hand, act D strongly decreased incorporation of 3H-uridine into RNA. Short-term regulation of thyroidal protein synthesis by TSH appears to be partly but not wholly dependent on neosynthesis of RNA. Hence regulation may partly occur at the translation level of protein synthesis.

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