title: The effect of retinoic acid on amino acid uptake and protein synthesis by lung fibroblasts.
abstract: The effect of retinoic acid (RA) on the uptake and utilization of extracellular amino acids by fetal lung fibroblasts was examined. RA decreased the incorporation of [3H]proline into collagen and other proteins. The effect was maximal at a RA concentration of 10(-5) M; smaller decreases were observed at a RA concentration of 10(-6) M. This decrease in collagen formation was associated with a large decrease in intracellular [3H] proline. The decrease in intracellular [3H]proline was first observed at 2 h following the addition of RA to cell cultures. Transport studies employing radiolabeled amino acids revealed that RA decreased the uptake of proline, 2-aminoisobutyric acid, and 2-(methylamino)isobutyric acid but not leucine or methionine. Kinetic analysis of 2-aminoisobutyric acid uptake indicated that this effect was mediated primarily by an increase in apparent Km, with a lesser decrease in Vmax, RA-induced inhibition of proline uptake was not abolished by the presence of cycloheximide nor by pretreatment with indomethacin. Na+,K(+)-ATPase activity was not affected by RA treatment. These results suggest that RA modulates protein production in fibroblasts by altering the function of the Na(+)-dependent A transport system for amino acid uptake.
authors.affiliation: Pulmonary Center, Boston University School of Medicine, Massachusetts 02118.
authors.forename: M
authors.initials: M
authors.lastname: Krupsky
authors.forename: A
authors.initials: A
authors.lastname: Fine
authors.forename: J L
authors.initials: JL
authors.lastname: Berk
authors.forename: R H
authors.initials: RH
authors.lastname: Goldstein
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000621:Aminoisobutyric Acids / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007930:Leucine / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D011392:Proline / Q000378:metabolism; D014176:Protein Biosynthesis; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D000596:Amino Acids; D000621:Aminoisobutyric Acids; C100049:2-aminoisobutyric acid; D014212:Tretinoin; D003513:Cycloheximide; D011392:Proline; D007930:Leucine; D007213:Indomethacin