Carole Evans

Alcoholic cardiomyopathy II. The inhibition of cardiac microsomal protein synthesis by acetaldehyde

Abstract Previous studies in this laboratory had shown that while ethanol at levels of 200 to 300 mg 100 ml had no effect on cardiac protein synthesis, acetaldehyde ( 3.5 mg 100 ml or 0.8 m m ) markedly inhibited cardiac protein synthesis in the intact heart in vitro. In order to localize further the action of acetaldehyde and to separate the protein synthetic effects from contractile function, studies on cell free systems with cardiac muscle microsomes were carried out at concentrations of acetaldehyde seen in humans after moderate ethanol ingestion. There was a significant reduction of microsomal protein synthesis even at these levels of acetaldehyde. Thus, with an acetaldehyde concentration of 0.53 mg 100 ml (0.12 m m ) the protein synthesis was reduced to 52 ± 5.3% of the control microsomes. With acetaldehyde concentrations of 0.13 to 0.26 mg 100 ml (0.03 to 0.06 m m ), the microsomal protein synthesis was 65 ± 8.6% of the controls. The differences from the controls were statistically significant. These data show that at concentrations seen in humans following ethanol ingestion, acetaldehyde interferes with normal cardiac protein synthesis independent of contractile action and thus may play a role in the ultimate development of ethanolic cardiomyopathy.

Metabolism of D-galactose to D-glucuronic acid, L-gulonic acid and L-ascorbic acid in normal and barbital-treated rats.

Abstract 1. 1. In vivo experiments in rats showed that D -[1- 14 C]galactose was better than D -[1- 14 C]glucose as a precursor of D -glucuronic acid, L -gulonic acid and L -ascorbic acid. The conversion of D -[1- 14 C]galactose to D -glucuronic acid and L -gulonic acid was demonstrated in rat-liver homogenate. The results presented are in accord with the biosynthesis of L -ascorbic acid via the uridine nucleotides. 2. 2. The administration of barbital to rats stimulated the in vivo conversion of D -[1- 14 C]galactose to D -glucuronic acid, L -gulonic acid and L -ascorbic acid. Enhanced formation of D -glucuronic acid from D -[1- 14 C]galactose was also observed in liver homogenates from rats pretreated with Chloretone. 3. 3. Formation of D -galacturonic acid from D -galactose in vivo was not detected in rats.

Alterations in Albumin Metabolism after Serum and Albumin Infusions

The intravenous administration of whole serum or of serum albumin results in a temporary increase in the concentration of circulating protein; the rate of return toward preinfusion levels depends upon the state of protein depletion or pool size and upon the rates of synthesis and degradation of albumin (1-6). Much of the infused protein can be accounted for by increased nitrogen excretion in the urine (2-4); the remainder has been assumed to be stored in intravascular or extravascular areas (1-6). The rate of disappearance of tracer-labeled homologous and heterologous albumin from plasma has been observed to increase during the infusion of whole serum or of serum albumin (6-7). Thus, although there is an increase in protein degradation associated with at least a temporary storage of protein, observations on the changes in endogenous protein synthesis and degradation that might follow such infusions are not available. The effects of prolonged infusions of pooled homologous serum or salt-poor human serum albumin on albumin metabolism in rabbits tolerant to human albumin are reported in the present study.

The effect of pressure or flow stress on right ventricular protein synthesis in the face of constant and restricted coronary perfusion.

Cardiac stress produced by hypertension or excess volume loading results in different types of hypertrophy. Elevated left ventricular pressure rapidly results in increased myocardial protein synthesis in vivo and in vitro, but such rapid alterations are not consistently seen in volume loading. The difference in response is difficult to clarify since it is not possible to effect alterations in left ventricular pressure or perfusion without profoundly affecting coronary perfusion. The present study describes cardiac protein synthesis in the right ventricle of the young guinea pig heart in vitro by utilizing a perfusion model in which the right ventricle could be stressed by elevations of pressure or volume loading in the presence of constant and restricted coronary perfusion. With coronary flow maintained at 4 ml/min per heart equivalent to 25 ml/min/g dry wt, an increase in right ventricular pressure from normal levels of 3 mm Hg to 11 mm Hg resulted in a 60 percent increase of myocardial incorporation of (14C)lysine into protein. However, with further increases of right ventricular pressure to 22 mm Hg, protein synthesis dropped back to normal levels. The falloff in protein synthesis was not due to decreased contractility, alterations in intracellular lysine pool specific activity, or alterations in distribution of coronary flow. a 60 percent increase in coronary perfusion was again associated with a similar response of protein synthesis to progressive elevations of pressure despite a rise in the ATP levels and a fall in lactate production. Thus, a deficiency of O2 did not entirely explain the decline of protein synthesis with maximal pressures. At all levels of coronary perfusion, volume loading for 3 h did not result in increased protein incorporation of (14C)lysine. The studies support a relationship between ventricular pressure and protein synthesis unrelated to coronary flow per se. A pressure receptor triggering protein synthesis within the ventricular wall is postulated. Such a relationship is not apparent in short-term volume loading in vitro.

Conversion of myo-inositol to d-glucuronic acid and l-gulonic acid in the rat

Abstract The metabolism of randomly labeled [3H]myo-inositol and uniformly labeled [14C]myoinositol has been investigated in rats. The results indicate that inositol is converted to d -glucoronic acid and l -gulonic acid. Formation of l -ascorbic acid and of l -glucuronic acid from inositol was not detected.

Problems in evaluating cardiac protein synthesis

Abstract How significant are present measurements of cardiac protein synthesis? In the heart, alterations in protein synthesis have been reported to accompany changes in organ size and gross structure, but the mechanisms involved in altering the synthesis and the significance of these alterations in heart muscle in adaptation to stress (defined as an influence of an adverse force or strain) have not been easily clarified. The determination of cardiac protein synthesis presents many problems some of which are inherent in the methodologies used and others in the complexities of the protein synthetic process itself, and examination of these problems is necessary in any evaluation of synthesis.