Glycosaminoglycan synthesis in amiodarone-induced pulmonary fibrosis
Thesis/Dissertation
·
OSTI ID:6527301
Glycosaminoglycans (GAG) have previously been demonstrated to be synthesized in greater than normal amounts following a single intratracheal insufflation of bleomycin in hamsters. This suggests that GAG may play a role in the propagation of pulmonary fibrotic reactions. To further test this hypothesis, GAG synthesis was studied in a new hamster model of interstitial lung injury, induced by the cardiac drug, aminodarone. Animals received a single intratracheal instillation of 1.25 mg aminodarone. At 4, 9, and 21 days post-insufflation, the animals were sacrificed, their lungs removed, and 1 mm fragments placed in explant culture for 6 hours at 37/sup 0/C in the presence of /sup 35/S-sulfate. The labeled GAG were isolated and measured for /sup 35/S incorporation. The author then isolated the hexosamine portions of the respective GAGs, Heparan Sulfate (HEP S), Chondroitin-6-Sulfate (Ch-6-S) and Chondroitin-4-Sulfate and Dermatan Sulfate (CH-4-S and DS) using the enzyme ABC and paper chromatography. They also studied the GAG content and distribution in hamster lung fibroblasts incorporated with /sup 35/S for 48 hours and subjected to either 0, 0.01 mg, 0.1 mg, or 1 mg of aminodarone. GAG synthesis is increased at an early stage following the induction of lung injury by aminodarone and remains elevated for a 3 week period. The change in GAG distribution boards elevated CH-4-S and DS may be characteristic of interstitial diseases in general. The GAGs that are synthesized by fibroblasts may be responsible for the increased CH-4-S and DS synthesis.
- Research Organization:
- Columbia Univ., New York (USA)
- OSTI ID:
- 6527301
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOSYNTHESIS
BODY
CARBOHYDRATES
CARDIOVASCULAR AGENTS
DAYS LIVING RADIOISOTOPES
DOSE-RESPONSE RELATIONSHIPS
DRUGS
EVEN-ODD NUCLEI
FIBROSIS
GLUCOPROTEINS
HAMSTERS
ISOTOPES
LIGHT NUCLEI
LUNGS
MAMMALS
NUCLEI
ORGANIC COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
PATHOGENESIS
PATHOLOGICAL CHANGES
PROTEINS
RADIOISOTOPES
RESPIRATORY SYSTEM
RODENTS
SACCHARIDES
SULFATES
SULFUR 35
SULFUR COMPOUNDS
SULFUR ISOTOPES
SYNTHESIS
UPTAKE
VERTEBRATES
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOSYNTHESIS
BODY
CARBOHYDRATES
CARDIOVASCULAR AGENTS
DAYS LIVING RADIOISOTOPES
DOSE-RESPONSE RELATIONSHIPS
DRUGS
EVEN-ODD NUCLEI
FIBROSIS
GLUCOPROTEINS
HAMSTERS
ISOTOPES
LIGHT NUCLEI
LUNGS
MAMMALS
NUCLEI
ORGANIC COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
PATHOGENESIS
PATHOLOGICAL CHANGES
PROTEINS
RADIOISOTOPES
RESPIRATORY SYSTEM
RODENTS
SACCHARIDES
SULFATES
SULFUR 35
SULFUR COMPOUNDS
SULFUR ISOTOPES
SYNTHESIS
UPTAKE
VERTEBRATES