Degradation of collagen in lung tissue slices exposed to hyperoxia.
Exposure of animals to oxidant gases produces a mild emphysema, and O2-derived free radicals are capable of degrading connective tissues in vitro. It is postulated that degradation of connective tissue by O2-derived free radicals leads to emphysema in these models. To determine whether exposure of lung tissue slices to an oxidant gas results in degradation of collagen and to investigate factors mediating this degradation, we exposed lung tissue slices from normal rats to hyperoxia (95% O2, 5% CO2) and measured hydroxyproline release into the medium. After a 4-h exposure, the hydroxyproline released was 5.3 +/- 0.2 micrograms/g lung tissue (n = 10) in normoxia and 8.1 +/- 0.6 micrograms/g tissue (n = 13) in hyperoxia (p less than 0.05), suggesting degradation of collagen. The addition of 0.1% trypsin to the initial incubation medium caused a synergistic increase in hydroxyproline release from O2-exposed slices: normoxia/trypsin, 46.2 +/- 3.6 micrograms/g tissue (n = 10); hyperoxia/trypsin, 61.4 +/- 3.6 micrograms/g tissue (n = 11) (p less than 0.05). The addition of proteinase inhibitors completely suppressed the O2-induced release of hydroxyproline, suggesting that proteolytic enzymes are involved in hyperoxia-mediated degradation of lung collagen.
D000818:Animals; D003094:Collagen / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D005609:Free Radicals; D006909:Hydroxyproline / Q000378:metabolism; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D003012:Microbial Collagenase / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology*; D011506:Proteins / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D015843:Serpins; D014357:Trypsin / Q000494:pharmacology
D005609:Free Radicals; D011506:Proteins; D015843:Serpins; D003094:Collagen; D003513:Cycloheximide; D007770:L-Lactate Dehydrogenase; D014357:Trypsin; D003012:Microbial Collagenase; D006909:Hydroxyproline; D010100:Oxygen