Ozone, but not nitrogen dioxide, fragments elastin and increases its susceptibility to proteolysis.
The effects of ozone (O3) and nitrogen dioxide (NO2) on the solubility and proteolytic susceptibility of elastin were examined to better understand how these oxidant air pollutants might damage the lung. In vitro O3 exposures at pH 7.4 resulted in the complete solubilization of elastin, but NO2 had no effect on solubility. The initial solubilization rate was 65 micrograms/mumol of O3, which increased to 150 micrograms/mumol in the midregion of a sigmoidal solubilization curve. Peptide fragments of the O3-solubilized elastin ranged in size from 5 to 20 kD. The conversion of insoluble elastin into soluble fragments by O3 was not due to the destruction of desmosine crosslinks. The effect of O3 on the proteolytic susceptibility of elastin was measured using insoluble elastin recovered from exposures that resulted in 5.3%, 12.8%, and 26.3% solubilization. Human neutrophil elastase (HNE) digested the remaining insoluble elastin samples 4.3, 6.0, and 9.8 times faster than unexposed elastin. In contrast, NO2-exposed elastin was no more susceptible to digestion by HNE. Ascorbate, EDTA, and uric acid reduced the proteolytic susceptibility of O3-exposed elastin, but mannitol afforded no protection. These findings indicate that the inhalation of O3 may contribute to lung disease by directly damaging elastin and by increasing its susceptibility to proteolysis, whereas NO2 probably damages lungs via alternative mechanisms.
Winters
R S
RS
Department of Biochemistry, J. H. Quillen College of Medicine, East Tennessee State University, Johnson City 37604.
Burnette-Vick
B A
BA
Johnson
D A
DA
D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002417:Cattle; D004549:Elastin / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D019272:Leukocyte Elastase / Q000378:metabolism; D008173:Lung Diseases, Obstructive / Q000201:enzymology / Q000209:etiology; D009504:Neutrophils / Q000201:enzymology; D009585:Nitrogen Dioxide / Q000633:toxicity*; D010126:Ozone / Q000633:toxicity*; D010196:Pancreatic Elastase / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000187:drug effects / Q000378:metabolism; D012995:Solubility
D000393:Air Pollutants; D000975:Antioxidants; D010446:Peptide Fragments; D010126:Ozone; D004549:Elastin; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D009585:Nitrogen Dioxide