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Induction of hepatic synthesis of serum amyloid A protein and actin
Abstract:
Major changes in the mRNA population of murine liver occur after administration of bacterial lipopolysaccharide, an agent that causes increases in the concentrations of acute-phase serum proteins. The mRNA for one of these, serum amyloid A, is increased at least 500-fold compared to the normal level. It becomes one of the most abundant hepatic mRNAs, and serum amyloid A synthesis comprises about 2.5% of total hepatic protein synthesis in the acute-phase response. Its synthesis is tissue-specific in that amyloid A mRNA was not detected in the kidney, an important site of amyloid fibril accumulation. The protein synthesized in largest amount by acute-phase liver tissue in culture is cytoplasmic actin. Its relative rate of synthesis is increased about 5-fold compared to the normal tissue; that of serum albumin is decreased to about one-third of its normal rate. The concentration of mRNA for serum albumin is decreased by a similar amount. Starting with induced liver RNA, we have constructed a recombinant plasmid containing most of the DNA sequence encoding the serum amyloid A polypeptide.
Insights
Bacterial lipopolysaccharide dramatically alters liver mRNA, significantly increasing serum amyloid A (SAA) mRNA levels for acute-phase protein production. This study also details changes in actin and albumin mRNA during this response.
Area of Science:
- Biochemistry
- Molecular Biology
- Immunology
Background:
- Bacterial lipopolysaccharide (LPS) triggers acute-phase responses in the liver, leading to altered protein synthesis.
- Acute-phase serum proteins, such as serum amyloid A (SAA), are significantly upregulated during inflammation.
Purpose of the Study:
- To investigate the changes in hepatic mRNA populations following LPS administration.
- To quantify the induction of SAA mRNA and its impact on overall protein synthesis.
- To examine the tissue specificity of SAA mRNA expression and its role in amyloidosis.
Main Methods:
- Administration of bacterial lipopolysaccharide (LPS) to mice.
- Analysis of murine liver mRNA populations using molecular techniques.
- Quantification of specific protein synthesis in cultured acute-phase liver tissue.
- Construction of a recombinant plasmid for SAA DNA sequence encoding.
Main Results:
- LPS administration caused major changes in liver mRNA, with a >500-fold increase in SAA mRNA.
- SAA synthesis constituted approximately 2.5% of total hepatic protein synthesis.
- Cytoplasmic actin synthesis increased ~5-fold, while serum albumin synthesis decreased to one-third of normal levels.
- SAA mRNA was detected in the liver but not in the kidney.
Conclusions:
- LPS induces a significant and specific increase in hepatic SAA mRNA during the acute-phase response.
- Changes in mRNA levels directly correlate with altered protein synthesis rates for SAA, actin, and albumin.
- The tissue-specific expression of SAA mRNA highlights its role in hepatic acute-phase reactions rather than kidney amyloid deposition.