title: Regulation of sulfated glycosaminoglycan production by prostaglandin E2 in cultured lung fibroblasts.
abstract: Prostaglandin E2 (PGE2) has been shown to increase the synthesis of hyaluronic acid in cultured fibroblasts by increasing the activity of hyaluronate synthetase, a group of plasma membrane-bound synthetic enzymes. We examined whether PGE2 also increased the activity of those enzyme systems involved in the synthesis of sulfated glycosaminoglycan in the human embryonic lung fibroblast. Exposure of cells to PGE2 resulted in dose-dependent increases in glucosamine incorporation into all sulfated glycosaminoglycan subtypes. PGE2 at 10(-7) mol/L increased total glycosaminoglycan per dish to 21.6 +/- 3.1 micrograms versus 12.0 +/- 2.5 micrograms in control untreated cultures. Stimulation of endogenous PGE2 production by bradykinin had a similar effect on glycosaminoglycan synthesis. To examine whether PGE2 affected sulfated glycosaminoglycan protein core production, cells were labeled with tritiated glucosamine in the presence of cycloheximide. Under these conditions, incorporation of radiolabel into all glycosaminoglycan subtypes was reduced. However, when exogenous sulfated glycosaminoglycan chain initiator (p-nitrophenyl beta-D-xyloside) was added, incorporation of tritiated glucosamine into sulfated glycosaminoglycan increased but not to levels found in control cultures. Application of PGE2 to cultures treated with cycloheximide alone, or to cultures treated with cycloheximide plus xyloside, increased tritiated glucosamine incorporation into chondroitin, dermatan sulfate, and to a lesser extent into heparan sulfate. We conclude that PGE2 stimulates synthesis of all sulfated glycosaminoglycan even in the absence of new protein core production, probably by increasing activities of sulfated glycosaminoglycan synthetase enzymes. PGE2 stimulation of heparan sulfate synthesis is partially dependent on the availability of heparan sulfate-specific protein core.
authors.affiliation: Pulmonary Center, Boston University School of Medicine, MA.
authors.forename: J B
authors.initials: JB
authors.lastname: Karlinsky
authors.forename: R H
authors.initials: RH
authors.lastname: Goldstein
mesh_terms: D001920:Bradykinin / Q000494:pharmacology; D002460:Cell Line; D002809:Chondroitin Sulfates / Q000096:biosynthesis; D003513:Cycloheximide / Q000494:pharmacology; D003871:Dermatan Sulfate / Q000096:biosynthesis; D015232:Dinoprostone / Q000494:pharmacology*; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005944:Glucosamine / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006027:Glycosides / Q000494:pharmacology; D006497:Heparan Sulfate / Q000096:biosynthesis; D006801:Humans; D006820:Hyaluronic Acid / Q000096:biosynthesis; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung; D013462:Sulfur Radioisotopes; D014316:Tritium
chemical_list: D001920:Bradykinin; D002809:Chondroitin Sulfates; D003513:Cycloheximide; D003871:Dermatan Sulfate; D015232:Dinoprostone; D005944:Glucosamine; D006025:Glycosaminoglycans; D006027:Glycosides; D006497:Heparan Sulfate; D006820:Hyaluronic Acid; D007213:Indomethacin; D013462:Sulfur Radioisotopes; D014316:Tritium; C010807:xylosides; C013786:A73025