Aortic perfusion pressure as a determinant of cardiac protein synthesis

1984 ◽  
Vol 246 (3) ◽  
pp. C247-C258 ◽  
Author(s):  
Y. Kira ◽  
P. J. Kochel ◽  
E. E. Gordon ◽  
H. E. Morgan
Keyword(s):  
Protein Synthesis ◽  
Oxygen Consumption ◽  
Perfusion Pressure ◽  
Energy Charge ◽  
Creatine Phosphate ◽  
Aortic Pressure ◽  
Cardiac Contraction ◽  
Adenylate Energy Charge ◽  
Rat Hearts ◽  
Pressure Development

Mechanical parameters and intracellular mediators that may control protein synthesis have been studied in isolated rat hearts subjected to increased aortic pressure or induced to perform cardiac work. Elevation of aortic pressure from 60 to 120 mmHg in Langendorff preparations with glucose, glucose plus insulin, or pyruvate raised the rate of protein synthesis during the 2nd h of perfusion. These effects involved faster rates of both peptide chain initiation and elongation. In working hearts supplied glucose or glucose plus insulin, higher rate of synthesis were observed in both the 1st and 2nd h of perfusion, compared with Langendorff preparations perfused at 60 mmHg. Intracellular levels of glucose 6-phosphate, ATP/ADP ratio, adenylate energy charge, or creatine phosphate/creatine did not correlate with the rate of protein synthesis in beating control hearts. When ventricular pressure development was prevented by ventricular draining and hearts were arrested with tetrodotoxin, protein synthesis still increased as a function of perfusion pressure. Oxygen consumption increased as aortic pressure was raised in beating-drained hearts but was unaffected in arrested-drained hearts. These results indicate that intraventricular pressure development, cardiac contraction, oxygen consumption, glucose 6-phosphate, energy availability, and coronary flow could be dissociated from the stimulatory effect of higher aortic pressures on protein synthesis and suggested that stretch of the ventricular wall, as a consequence of increased aortic pressure, could be the mechanical parameter most closely related to the increase in protein synthesis.

Aortic pressure as a determinant of cardiac protein degradation

1986 ◽  
Vol 250 (6) ◽  
pp. C932-C938 ◽  
Author(s):  
E. E. Gordon ◽  
Y. Kira ◽  
L. M. Demers ◽  
H. E. Morgan
Keyword(s):  
Protein Degradation ◽  
Creatine Phosphate ◽  
Aortic Pressure ◽  
Inhibitory Effect ◽  
Cardiac Contraction ◽  
Rat Hearts ◽  
Pressure Development ◽  
Calcium Availability ◽  
Intracellular Mediators ◽  
Control Protein

Mechanical parameters and intracellular mediators that may control protein degradation were studied in isolated rat hearts subjected to increased aortic pressure. Elevation of aortic pressure from 60 to 120 mmHg in Langendorff preparations provided glucose or pyruvate as substrate decreased the rate of protein degradation during the second hour of perfusion. Intracellular contents of ATP or creatine phosphate or the creatine phosphate/creatine ratio did not indicate that energy depletion accounted for these effects. When ventricular pressure development was prevented by ventricular draining, and hearts were arrested with tetrodotoxin, protein degradation still decreased as aortic pressure was raised. The effect of elevated aortic pressure on proteolysis was unchanged when perfusate calcium concentrations were 0.6, 3.0, or 5.1 mM, or when indomethacin or meclofenamate was added to the perfusion buffer. These results provided no evidence to indicate that intraventricular pressure development or cardiac contraction was responsible for the inhibitory effect of increased aortic pressure on protein degradation. Instead, they suggested that stretch of the ventricular wall, as a consequence of increased aortic pressure, could be the mechanical parameter most closely related to the restraint on proteolysis. No evidence was obtained that the lower rate of degradation depended on energy or calcium availability or prostaglandin synthesis.

Insulin effects on protein synthesis are independent of glucose and energy metabolism

1983 ◽  
Vol 245 (1) ◽  
pp. C133-C143 ◽  
Author(s):  
K. E. Flaim ◽  
P. J. Kochel ◽  
Y. Kira ◽  
K. Kobayashi ◽  
E. T. Fossel ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Energy Metabolism ◽  
Energy Charge ◽  
Creatine Phosphate ◽  
Peptide Chain ◽  
Maximal Effect ◽  
Adenylate Energy Charge ◽  
Phosphate Content ◽  
Chain Initiation ◽  
Rat Hearts

Protein synthesis was accelerated in rat hearts that were provided insulin compared with provision of glucose or pyruvate alone or a mixture of glucose and pyruvate. The faster synthetic rates were accompanied by a reduction in numbers of ribosomal subunits, indicating that peptide chain initiation was accelerated relative to elongation/termination. In hearts supplied glucose, 65% of the maximal effect on protein synthesis was achieved by addition of 1.7 X 10(-10) M insulin, but significant effects on glucose uptake as well as on tissue contents of glucose 6-phosphate and creatine phosphate were obtained only with 7 X 10(-10) M insulin. Addition of glucose to perfusates containing pyruvate did not accelerate protein synthesis, although the glucose 6-phosphate content was raised. Similarly, the stimulatory effects of insulin on protein synthesis in hearts supplied pyruvate did not depend on changes in glucose 6-phosphate content, creatine phosphate/creatine, ATP/ADP, or adenylate energy charge. These studies indicate that insulin accelerated peptide-chain initiation and protein synthesis in rat heart by mechanisms independent of the hormone's effect on glucose or energy metabolism.

Effect of intraventricular pressure on protein synthesis in arrested rat hearts

1986 ◽  
Vol 251 (1) ◽  
pp. C95-C98 ◽  
Author(s):  
X. P. Xenophontos ◽  
E. E. Gordon ◽  
H. E. Morgan
Keyword(s):  
Protein Synthesis ◽  
Left Ventricle ◽  
Ribosomal Subunit ◽  
Creatine Phosphate ◽  
Aortic Pressure ◽  
Ventricular Wall ◽  
Intraventricular Pressure ◽  
Chain Initiation ◽  
Rat Hearts

A modification of the Langendorff technique for perfusion of rat hearts was developed to allow a constant intraventricular pressure to be imposed on the left ventricle of arrested-catheterized hearts. This model was used to assess effects of increased aortic (60 and 120 mmHg) and intraventricular (0 and 25 mmHg) pressures on the rate of protein synthesis between 70 and 130 min of perfusion and on contents of ATP and creatine phosphate (creatine-P) in ventricles. Rates of protein synthesis in atria also were measured. Increased intraventricular or aortic pressure elevated the rate of protein synthesis (41%) compared with hearts supplied an aortic pressure of 60 mmHg and an intraventricular pressure of 0 mmHg. Higher intraventricular pressure also decreased the ribosomal subunit content. No change in the rate of protein synthesis was observed when intraventricular pressure was raised in hearts supplied an aortic pressure of 120 mmHg. Rates of atrial protein synthesis and contents of ATP and creatine-P were unchanged by elevations of either intraventricular or aortic pressure. These experiments indicate that stretch of the ventricular wall due to higher intraventricular or aortic pressure accelerated protein synthesis by maintaining the in vivo balance between rates of peptide chain initiation and elongation.

Peroxynitrite contributes to spontaneous loss of cardiac efficiency in isolated working rat hearts

1999 ◽  
Vol 276 (6) ◽  
pp. H1861-H1867 ◽  
Author(s):  
Peter Ferdinandy ◽  
Donna Panas ◽  
Richard Schulz
Keyword(s):  
Protein Synthesis ◽  
Oxygen Consumption ◽  
Contractile Function ◽  
Tca Cycle ◽  
Protein Synthesis Inhibitor ◽  
Mechanical Function ◽  
Cardiac Work ◽  
Synthesis Inhibitor ◽  
Atp Production ◽  
Rat Hearts

We examined the mechanism of the time- and protein synthesis-dependent decline in cardiac mechanical function in isolated working rat hearts. Hearts were perfused with Krebs-Henseleit buffer for 120 min in the presence or absence of the protein synthesis inhibitor cycloheximide (CX; 10 μM). Cardiac work remained stable for 60 min and then spontaneously decreased during 60–120 min of perfusion. This was accompanied by an increase in myocardial inducible nitric oxide synthase (iNOS) and xanthine oxidase (XO) activities and enhanced dityrosine formation in the perfusate, an indicator of peroxynitrite generation. CX markedly attenuated the loss in contractile function and prevented the increase in iNOS and XO activities and dityrosine level. Despite the decline in cardiac work in control hearts, the coupling between tricarboxylic acid (TCA) cycle activity and oxygen consumption remained constant in both groups. ATP, creatine phosphate, and glycogen levels were not different between control and CX groups and did not differ over 120 min of perfusion. We concluded that the delayed and spontaneous loss in myocardial mechanical function in isolated working rat hearts is 1) attenuated by CX treatment, 2) accompanied by a concomitant increase in both iNOS and XO activities and peroxynitrite generation in the heart, and 3) not dependent on a direct impairment in myocardial ATP production, myocardial oxygen consumption, or TCA cycle acetyl-CoA production but may be due to an inefficiency of the heart to utilize ATP for contractile work.

Differential effects of cysteine on protein and coenzyme A synthesis in rat heart

1984 ◽  
Vol 247 (1) ◽  
pp. C99-C106 ◽  
Author(s):  
B. H. Chua ◽  
K. E. Giger ◽  
B. J. Kleinhans ◽  
J. D. Robishaw ◽  
H. E. Morgan
Keyword(s):  
Protein Synthesis ◽  
Rat Heart ◽  
Coenzyme A ◽  
Pantothenic Acid ◽  
Fold Increase ◽  
Creatine Phosphate ◽  
Aortic Pressure ◽  
Protective Agent ◽  
Bicarbonate Buffer ◽  
Perfused Rat Heart

The effect of cysteine availability on protein and coenzyme A (CoA) synthesis in perfused rat heart was incompletely evaluated in earlier experiments because rapid conversion of cysteine to cystine occurred when the perfusion buffer was oxygenated. This conversion was minimized by addition of an excess of reducing agents such as dithiothreitol or mercaptodextran or by provision of bathocuproine disulfonate, a copper chelator. Dithiothreitol was not a suitable protective agent because it reduced ATP and creatine phosphate contents. Perfusion of hearts with [35S]cystine or [35S]cysteine in the presence of mercaptodextran resulted in a 22-fold or 5-fold increase, respectively, in incorporation of [35S] into protein and a 5-fold or 8-fold increase, respectively, in incorporation into CoA compared with hearts supplied [35S]cystine or [35S]cysteine without the reducing agent. When compared with hearts perfused at an aortic pressure of 90 mmHg with bicarbonate buffer that contained 15 mM glucose, 25 mU insulin/ml, 0.4 mM [14C]phenylalanine, no cysteine and plasma levels of other amino acids, provision of 0.09 or 0.2 mM cysteine alone or in the presence of mercaptodextran, or bathocuproine disulfonate enhanced rates of protein synthesis 16-35%. When 0.2 mM cysteine was added to bicarbonate buffer containing 7 microM pantothenic acid, supplementation with mercaptodextran or bathocuproine disulfonate was required to raise CoA content. These results indicated that an exogenous supply of cysteine was needed to maintain maximal rates of protein and CoA synthesis in the perfused rat heart. Protective compounds were required to obtain the cysteine effect on CoA but not on protein synthesis.

Contracture of isolated rat heart cells on anaerobic to aerobic transition

1982 ◽  
Vol 242 (6) ◽  
pp. H1022-H1030 ◽  
Author(s):  
C. Hohl ◽  
A. Ansel ◽  
R. Altschuld ◽  
G. P. Brierley
Keyword(s):  
Rat Heart ◽  
Adenine Nucleotide ◽  
Energy Charge ◽  
Creatine Phosphate ◽  
Isolated Rat Heart ◽  
Heart Cells ◽  
Adenylate Energy Charge ◽  
Adult Rat ◽  
Oxygen Paradox ◽  
Adenine Nucleotide Pool

Adult rat heart myocytes prepared by collagenase perfusion show a progressive loss of adenylate energy charge and total adenine nucleotide as a function of time of anaerobic incubation in the absence of glucose. Re-aeration of the rod-shaped anaerobic cells produces a population of viable rounded cells in hypercontracture. The round cells show extensive morphological dislocations but remain metabolically competent in that they 1) restore adenosine 5'-triphosphate levels to the extent permitted by the depleted adenine nucleotide pool: 2) reestablish a low Na+-K+ ratio; and 3) restore creatine phosphate to 73% of control. The hypercontracture on re-aeration of anaerobic myocytes closely resembles an analogous contracture of heart cells in situ produced when hypoxic perfused hearts are reoxygenated, the so-called "oxygen paradox." Both processes are eliminated by inclusion of glucose during the anaerobic phase and by inhibitors of respiration and uncouplers of oxidative phosphorylation added before reoxygenation. Mitochondria in the hypercontracted myocytes retain high acceptor control ratios. Contracture on re-aeration occurs to nearly the same extent in the presence of either mM Ca2+ or 0.1 mM EGTA. Contracture appears related to dislocations in intracellular Ca metabolism that result from the declining energy charge and depleted nucleotide pool produced during anoxic incubation.

scholarly journals Relationship Between Protein Synthesis and Secretion in Liver Cells and the State of the Adenine Nucleotide System

1979 ◽  
Vol 32 (3) ◽  
pp. 299 ◽  
Author(s):  
Kaylene Edwards ◽  
Jörg Urban ◽  
Gerhard Schreiber
Keyword(s):  
Protein Synthesis ◽  
Oxidative Phosphorylation ◽  
Protein Secretion ◽  
Liver Cell ◽  
Maximum Rate ◽  
Adenine Nucleotide ◽  
Energy Charge ◽  
Adenylate Energy Charge ◽  
Atp Level ◽  
Atp Pool

Adenine nucleotide levels could be precisely and reproducibly adjusted in liver cell suspensions by partially depleting the ATP pool with D-fructose or glycerol. Thus, it was possible to quantitatively correlate rates of protein synthesis and secretion with intracellular levels of ATP and with derived parameters, such as the adenylate energy charge. Half the maximum rate of incorporation of leucine into protein was observed at an energy charge of 0�80, a ratio of ATP to ADP of 2�6, and an ATP level of 1�05 pmol per g of wet cells. Proteins were secreted with half the maximum rate at an energy charge of 0�85, a ratio of ATP to ADP of 3�1 and an ATP concentration of 1 �1 pmol per gof wet cells. Protein secretion dill not depend on continued synthesis. Inhibitors of oxidative phosphorylation inhibited protein secretion in addition to protein synthesis, in contrast to observations by other authors on liver slices.

AMP deaminase deficiency: Study of the human skeletal muscle purine metabolism during ischaemic isometric exercise

1987 ◽  
Vol 72 (4) ◽  
pp. 475-482 ◽  
Author(s):  
S. P. T. Sinkeler ◽  
R. A. Binkhorst ◽  
E. M. G. Joosten ◽  
R. A. Wevers ◽  
M. M. Coerwinkel ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Test ◽  
Adenine Nucleotide ◽  
Energy Charge ◽  
Isometric Exercise ◽  
Creatine Phosphate ◽  
Adenylate Energy Charge ◽  
Amp Deaminase ◽  
Control Subjects ◽  
Before And After

1. Muscle biopsies were taken from 10 control subjects and five AMP deaminase (AMPD) deficient individuals before and after an ischaemic isometric exercise test and analysed for purine nucleotide, NAD+, creatine phosphate (CP) and lactate content. 2. The decrease of ATP induced by the exercise test was significantly lower in the AMPD deficient patients than in the controls, but the decrease of creatine phosphate and the increase of lactate did not differ. There were no significant differences in the exertional performance level between patients and controls and no evidence was obtained of an increased energy expenditure per unit of performance in AMPD deficiency. 3. The AMPD deficient individuals were equally capable of maintaining a high adenylate energy charge (EC) as the control subjects, which indicates a normal regulation of the balance between ATP consumption and ATP regeneration. 4. ATP, ADP and total adenine nucleotide (TAN) but not AMP, were significantly elevated in the AMPD deficient patients as compared with the controls before as well as after the exercise test. This underlines the role of AMPD activity in the adenine nucleotide catabolism of skeletal muscle.

Faster ribosome synthesis induced by elevated aortic pressure in rat heart

1987 ◽  
Vol 252 (3) ◽  
pp. C323-C327 ◽  
Author(s):  
B. H. Chua ◽  
L. A. Russo ◽  
E. E. Gordon ◽  
B. J. Kleinhans ◽  
H. E. Morgan
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Ribosomal Protein ◽  
Total Protein ◽  
Rat Heart ◽  
Relative Rate ◽  
Plasma Concentrations ◽  
Aortic Pressure ◽  
Rat Hearts ◽  
Ribosomal Protein Synthesis

An increase in aortic pressure from 60 to 120 mmHg accelerated ribosomal protein synthesis in rat hearts during 1 or 2 h of labeling with 0.4 mM [3H]phenylalanine. When hearts were perfused with buffer that contained 20 mM glucose and normal plasma concentrations of 19 other amino acids without added insulin, ribosomal protein synthesis relative to the rate of total protein synthesis increased from approximately 0.22 to 0.36 and 0.30 as aortic pressure was raised from 60 to 120 mmHg during 1 or 2 h of labeling, respectively. With the addition of insulin, the relative rate of ribosomal protein synthesis averaged 0.33 at an aortic pressure of 60 mmHg and increased to 0.42 when aortic pressure was raised to 120 mmHg. These results indicate that elevation of aortic pressure has a preferential effect on synthesis of new ribosomes. This response appears to be an early and physiologically significant event in cardiac hypertrophy.

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