Regulation of Type I Collagen mRNA by Amino Acid Deprivation in Human Lung Fibroblasts
Autor: | Ping-Ping Kuang, Ronald H. Goldstein, Meir Krupsky |
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Rok vydání: | 1997 |
Předmět: |
Transcription
Genetic Glycine Retinoic acid Tretinoin Cycloheximide Biology Lung injury Biochemistry Dinoprostone chemistry.chemical_compound Protein biosynthesis medicine Humans RNA Messenger Amino Acids Prostaglandin E2 Lung Molecular Biology Cells Cultured chemistry.chemical_classification Messenger RNA Cell Biology Fibroblasts Molecular biology Amino acid Kinetics Gene Expression Regulation chemistry Collagen Type I collagen medicine.drug |
Zdroj: | Journal of Biological Chemistry. 272:13864-13868 |
ISSN: | 0021-9258 |
DOI: | 10.1074/jbc.272.21.13864 |
Popis: | The steady state levels of alpha1(I) collagen mRNA are decreased by retinoic acid and prostaglandin E2. These effector substances decrease the uptake of A system amino acids. We examined the effect of amino acid deprivation on the steady state levels of alpha1(I) collagen in human lung fibroblasts. Maintenance of fibroblasts in amino acid-free medium decreased alpha1(I) collagen mRNA levels by 29% at 24 h and 78% at 72 h. Frequent refeeding of cultures with amino acid-free medium resulted in more rapid decreases in intracellular amino acids and in alpha1(I) collagen mRNA levels. The decrease in alpha1(I) collagen mRNA levels was mediated by decreases in mRNA stability as assessed by a half-life determination using actinomycin D and by decreases in the rate of transcription as assessed by nuclear run-on assay. Treatment of fibroblasts with medium containing amino acids resulted in rapid restoration of alpha1(I) collagen mRNA levels. This increase in alpha1(I) collagen mRNA expression required protein synthesis as determined by cycloheximide sensitivity and was inhibited by prostaglandin E2. These data indicate that alpha1(I) collagen mRNA levels are sensitive to alterations in the amount of intracellular amino acids and suggest a potential mechanism whereby alpha1(I) collagen accumulation may be regulated independent of inflammatory mediators following lung injury. |
Databáze: | OpenAIRE |
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