Regulation of sulfated glycosaminoglycan production by prostaglandin E2 in cultured lung fibroblasts

Journal Article · Tue Aug 01 00:00:00 EDT 1989 · Journal of Laboratory and Clinical Medicine; (USA)

OSTI ID:5478922

Karlinsky, J B; Goldstein, R H ^[1]

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1. Boston Univ. School of Medicine, MA (USA)

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.

• OSTI ID: 5478922
• Journal Information: Journal of Laboratory and Clinical Medicine; (USA), Vol. 114:2; ISSN 0022-2143
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
GLYCOPROTEINS
BIOSYNTHESIS
LIGASES
ENZYME ACTIVITY
PROSTAGLANDINS
BIOCHEMICAL REACTION KINETICS
CYCLOHEXIMIDE
DOSE-RESPONSE RELATIONSHIPS
EMBRYOS
FIBROBLASTS
GLUCOSAMINE
GLYCOSIDES
HYALURONIC ACID
KININS
LUNGS
MAN
SULFATES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
AMINES
ANIMAL CELLS
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
BODY
CARBOHYDRATES
CONNECTIVE TISSUE CELLS
DRUGS
ENZYMES
FUNGICIDES
HEXOSAMINES
HEXOSES
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
MAMMALS
MONOSACCHARIDES
MUCOPOLYSACCHARIDES
ORGANIC COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
PEPTIDES
PESTICIDES
POLYPEPTIDES
POLYSACCHARIDES
PRIMATES
PROTEINS
REACTION KINETICS
RESPIRATORY SYSTEM
SACCHARIDES
SOMATIC CELLS
SULFUR COMPOUNDS
SYNTHESIS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques