Albumin synthesis by the perfused rat liver. A comparison of methods with special reference to the effect of dietary protein deprivation.
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ABSTRACT:
SUBMITTER: Hoffenberg R
PROVIDER: S-EPMC1176755 | biostudies-other | 1971 Apr
REPOSITORIES: biostudies-other
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Project description:Albumin synthesis was measured in the isolated perfused rat liver by using the livers of both well-fed and starved rats. Starvation markedly decreased albumin synthesis. The livers from starved rats were unable to increase synthesis rates after the addition to the perfusates of single amino acids or the addition of both glucagon and tryptophan. Arginine, asparagine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, threonine, tryptophan and valine, added together to ten times their normal peripheral blood concentrations, restored synthesis rates to normal. The plasma aminogram (i.e. the relative concentrations, of amino acids) was altered by depriving rats of protein for 48h. The use of blood from the deprived rats as perfusate, instead of normal blood, decreased albumin synthesis rates significantly by livers obtained from well-fed rats. The addition of single amino acids, including the non-metabolizable amino acid, alpha-aminoisobutyric acid, to the above mixture increased albumin synthesis rates to normal values. It is concluded that amino acids play an important role in the control of albumin synthesis and that more than one mechanism is probably involved.
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Project description:1. The isolated perfused rat liver was used to study degradation rates of plasma albumin, transferrin and fibrinogen. 2. Constant fractional rates were observed for all three proteins even when the albumin concentration was drastically increased by the addition of large amounts to the perfusate pool. 3. Livers taken from rats deprived of dietary protein for 14-18 days showed greatly diminished fractional catabolic rates for albumin when perfused with blood from similarly deprived animals. 4. These rates could be restored to near-normal values by adding albumin or by perfusing with blood from normally fed rats. 5. These findings are consistent with the theory of pinocytosis as a step in the degradation of plasma proteins by hepatic parenchymal cells.
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Project description:In rats fed on a protein-deficient diet, albumin synthesis as a percentage of total liver protein synthesis falls from the normal value of approx. 15% to about 8%. We have extracted total cytoplasmic RNA from individual rat livers and measured the concentration of active albumin mRNA by translation in a reticulocyte lysate system from which the endogenous mRNA had been removed [Pelham & Jackson (1976) Eur. J. Biochem. 67, 247-256]. In this messenger-dependent system it is possible to measure the synthesis of albumin as a proportion of the overall protein synthesis promoted by the addition of the hepatic RNA. The results show that the concentration of translatable albumin mRNA in samples of total cytoplasmic RNA from livers of protein-deficient rats is decreased markedly. These findings suggest that dietary protein supply affects selectively the synthesis and/or functional stability of albumin mRNA in rat liver.
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Project description:A major challenge in systems biology is to infer the parameters of regulatory networks that operate in a noisy environment, such as in a single cell. In a stochastic regime it is hard to distinguish noise from the real signal and to infer the noise contribution to the dynamical behavior. When the genetic network displays oscillatory dynamics, it is even harder to infer the parameters that produce the oscillations. To address this issue we introduce a new estimation method built on a combination of stochastic simulations, mass action kinetics and ensemble network simulations in which we match the average periodogram and phase of the model to that of the data. The method is relatively fast (compared to Metropolis-Hastings Monte Carlo Methods), easy to parallelize, applicable to large oscillatory networks and large (~2000 cells) single cell expression data sets, and it quantifies the noise impact on the observed dynamics. Standard errors of estimated rate coefficients are typically two orders of magnitude smaller than the mean from single cell experiments with on the order of ~1000 cells. We also provide a method to assess the goodness of fit of the stochastic network using the Hilbert phase of single cells. An analysis of phase departures from the null model with no communication between cells is consistent with a hypothesis of Stochastic Resonance describing single cell oscillators. Stochastic Resonance provides a physical mechanism whereby intracellular noise plays a positive role in establishing oscillatory behavior, but may require model parameters, such as rate coefficients, that differ substantially from those extracted at the macroscopic level from measurements on populations of millions of communicating, synchronized cells.
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Project description:Previous studies have demonstrated that autophagic vacuoles induced in hepatocytes of the perfused rat liver can be effectively separated from secondary lysosomes in self-generating gradients of colloidal silica/polyvinylpyrrolidone. Here we show that, as autophagy is increased by graded amino acid deprivation, the lysosomal marker N-acetyl-beta-D-glucosaminidase shifts progressively from dense to buoyant gradient fractions, an effect attributable to enhanced lysosome-autophagosome fusion and the formation of additional autolysosomes. Both the amount of the shift and the aggregate volume of autolysosomes were directly proportional to the increase in protein degradation above basal. Because the total quantity of protein sequestered in the vacuoles is also a direct function of deprivation-induced proteolysis, the relative specific activity of the marker enzyme in autolysosomes (enrichment) would be expected to remain constant over the full range of deprivation; numerical estimates of enrichment, in fact, did not differ from the mean (43.9) by more than 5%. The close correspondence between cytoplasmic sequestration and fusion was maintained, despite a greater than 3-fold increase in the average volume of individual vacuoles. This suggests the existence of an intrinsic regulatory mechanism which limits the number of fusions per vacuole, on the basis of information derived from vacuolar volume.
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