Biosynthesis of human acute-phase serum amyloid A protein (A-SAA) in vitro: the roles of mRNA accumulation, poly(A) tail shortening and translational efficiency
| Autor: | F C DeBeer, Jack T. Rogers, Diana M. Steel, Alexander S. Whitehead, M C DeBeer |
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| Jazyk: | angličtina |
| Rok vydání: | 1993 |
| Předmět: |
Carcinoma
Hepatocellular Apolipoprotein B Translational efficiency animal diseases Molecular Sequence Data Biochemistry Monocytes Downregulation and upregulation Drug Stability Polysome hemic and lymphatic diseases Protein biosynthesis Tumor Cells Cultured Humans RNA Messenger Molecular Biology Serum Amyloid A Protein Messenger RNA biology Base Sequence Interleukin-6 Liver Neoplasms Acute-phase protein Cell Biology Blotting Northern Molecular biology stomatognathic diseases Kinetics Culture Media Conditioned Protein Biosynthesis biology.protein Dactinomycin Electrophoresis Polyacrylamide Gel Poly A Research Article Interleukin-1 |
| Popis: | Human ‘acute-phase’ serum amyloid A protein (A-SAA) is a major acute-phase reactant (APR) and an apolipoprotein of high density lipoprotein 3 (HDL3). We have examined several parameters of A-SAA biosynthesis in PLC/PRF/5 hepatoma cells in response to monocyte conditioned medium (MoCM) and dual treatment with interleukin-1 beta and interleukin-6 (IL-1 beta + IL-6). Treatment of PLC/PRF/5 cells with MoCM or IL-1 beta + IL-6 caused a dramatic and rapid increase in A-SAA mRNA and protein synthesis; A-SAA mRNA was first detectable at 3 h, with peak levels reached by 24 h. A-SAA mRNA accumulation is accompanied by a gradual and homogeneous decrease in the length of the A-SAA poly(A) tail; the poly(A) tail shortening does not apparently affect the intrinsic stability of A-SAA mRNA. Analysis of RNA isolated from the ribonucleoprotein, monosome and polysome fractions of cytokine-treated PLC/PRF/5 cells showed that most A-SAA mRNA was associated with small polyribosomes, regardless of time post-stimulus, suggesting that the translational efficiency of A-SAA mRNA is constant throughout cytokine-driven induction. Moreover, the transit time of A-SAA protein out of the cell is also constant throughout the time course of induction. These data provide evidence of a paradox with regard to the transcriptional upregulation of A-SAA by IL-1 beta + IL-6 and the relative synthesis of A-SAA protein and suggest a role for post-transcriptional control of A-SAA biosynthesis during the acute phase. |
| Databáze: | OpenAIRE |
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