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Regulation of plasma acute-phase protein and albumin levels in the liver of scalded rats.

ABSTRACT: At 12 h after scalding of rats a doubling of the hepatocyte nuclear DNA content, which arose from the presence of additional complete genomes and not from amplification of genes coding for the major acute-phase proteins or albumin, was observed. Examination of relative transcription rates per control DNA mass revealed that alpha 1-acid-glycoprotein and cysteine-proteinase-inhibitor genes remained constitutive, alpha- and gamma-fibrinogen and haptoglobin genes underwent transcriptional activation for 290 and 339% respectively, whereas the relative transcription rate of albumin decreased to 65% of the control level. Along with these changes, the alpha 1-acid glycoprotein, cysteine-proteinase inhibitor and the fibrinogen mRNA concentrations increased about 500%, haptoglobin mRNA 250%, whereas the albumin mRNA concentration fell to 86% of the control. The regulation of the mRNA levels was assessed by comparing the relative change in transcription rates expressed per control DNA content with the relative changes of mRNA concentrations. We arrived at the conclusion that the concentrations of alpha 1-acid-glycoprotein and cysteine-proteinase-inhibitor mRNAs were predominantly regulated by a post-transcriptional mechanism, albumin mRNA by a transcriptional mechanism, and the fibrinogen and haptoglobin mRNAs by a combination of both. The degree of change of the serum levels of the examined proteins was similar to that of their mRNA concentrations and was the result of the complete use of the available RNA templates in protein synthesis.

SUBMITTER: Sevaljevic L

PROVIDER: S-EPMC1138417 | biostudies-other | 1989 Mar

REPOSITORIES: biostudies-other

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Project description:We defined the acute phase behaviour of a number of rabbit plasma proteins in studies (in vivo) and studied the effects of monokine preparations on their synthesis by rabbit primary hepatocyte cultures. Following turpentine injection, increased serum levels of C-reactive protein, serum amyloid A protein, haptoglobin, ceruloplasmin, and decreased concentrations of albumin were observed. In contrast to what is observed in man, concentrations of alpha 2-macroglobulin and transferrin were increased. Co-culture of primary hepatocyte cultures with lipopolysaccharide-activated human peripheral blood monocytes or incubation with conditioned medium prepared from lipopolysaccharide-activated human or rabbit monocytes resulted in dose-dependent induction of serum amyloid A, haptoglobin, ceruloplasmin and transferrin and depression of albumin synthesis, while C-reactive protein synthesis and mRNA levels remained unchanged. A variety of interleukin-1 preparations induced dose-dependent increases in the synthesis and secretion of serum amyloid A, haptoglobin, ceruloplasmin and transferrin and decreased albumin synthesis. Human recombinant tumour necrosis factor (cachectin) induced a dose-dependent increase in synthesis of haptoglobin and ceruloplasmin. In general, human interleukin-1 was more potent than mouse interleukin-1 and tumour necrosis factor. None of the monokines we studied had an effect on C-reactive protein synthesis or mRNA levels. These data confirm that C-reactive protein, serum amyloid A, haptoglobin and ceruloplasmin display acute phase behaviour in the rabbit, and demonstrate that, in contrast to their behaviour in man, alpha 2M and transferrin are positive acute phase proteins in this species. While both interleukin-1 and tumour necrosis factor regulate biosynthesis of a number of these acute phase proteins in rabbit primary hepatocyte cultures, neither of these monokines induced C-reactive protein synthesis. Comparison of these findings with those in human hepatoma cell lines, in which interleukin-1 does not induce serum amyloid A synthesis, suggests that the effect of interleukin-1 on serum amyloid A synthesis may be indirect.

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Regulation of plasma acute-phase protein and albumin levels in the liver of scalded rats.

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