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Levels of messenger ribonucleic acids for plasma proteins in rat liver during acute experimental inflammation
Abstract:
The levels of mRNA for plasma proteins and for metallothionein in rat liver during the acute-phase response were studied by hybridization to specific cDNA probes. The mRNA for alpha 2-macroglobulin, the beta-chain of fibrinogen, alpha 1-acid glycoprotein (so-called acute-phase reactants) reached a maximum level between 18 and 36 h after inducing an acute inflammation. The level of mRNA for metallothionein-I peaked earlier, after 12 h. The mRNA for transferrin showed a delayed increase with a broad maximum for its relative level after 36-60 h. The mRNA levels for albumin and alpha 2u-globulin (so-called negative acute-phase reactants) decreased, reaching a minimum of 25% of the normal level after 36 h (albumin) and after 72 h (alpha 2u-globulin). The ratios of the rates of incorporation of leucine into the proteins over the levels of their mRNA in liver changed only a little, indicating that the rates of synthesis of plasma proteins in the liver are regulated at the mRNA level during the acute-phase response to inflammation.
Insights
During acute-phase response, mRNA levels for inflammation-related proteins change dynamically in rat liver. Protein synthesis regulation primarily occurs at the messenger RNA level, influencing plasma protein production.
Area of Science:
- Molecular Biology
- Biochemistry
- Physiology
Background:
- The acute-phase response is a systemic reaction of the body to inflammation.
- Plasma protein synthesis in the liver is significantly altered during inflammation.
- Understanding gene expression regulation is crucial for comprehending these alterations.
Purpose of the Study:
- To investigate the dynamic changes in mRNA levels of various plasma proteins and metallothionein in rat liver during the acute-phase response.
- To determine the role of mRNA levels in regulating the synthesis rates of liver-produced proteins during inflammation.
Main Methods:
- Utilized hybridization techniques with specific cDNA probes to quantify mRNA levels.
- Studied mRNA expression in rat liver at various time points following induced acute inflammation.
- Analyzed the incorporation of leucine into proteins relative to mRNA levels.
Main Results:
- mRNA levels for positive acute-phase reactants (alpha 2-macroglobulin, fibrinogen beta-chain, alpha 1-acid glycoprotein) peaked between 18-36 hours post-inflammation.
- Metallothionein-I mRNA peaked earlier (12 hours), while transferrin mRNA showed a delayed increase (36-60 hours).
- mRNA levels for negative acute-phase reactants (albumin, alpha 2u-globulin) decreased significantly, reaching minimums at 36 and 72 hours, respectively.
- Ratios of protein synthesis rates to mRNA levels remained relatively constant, indicating mRNA-level regulation.
Conclusions:
- The synthesis of plasma proteins in the liver during the acute-phase response is primarily regulated at the mRNA level.
- Specific temporal patterns of mRNA expression underlie the differential regulation of acute-phase reactants and negative acute-phase reactants.