What does ozone react with at the air/lung interface? Model studies using human red blood cell membranes.
We exposed human red blood cell (RBC) membranes to low levels of ozone and measured the oxidative damage that occurs to the proteins and the unsaturated lipids that are present. Oxidative damage to proteins causes significant decreases in the content of thiol groups, the fluorescence of protein-tryptophan residues, and the activity of membrane-bound acetylcholinesterase. Oxidative damage to lipids causes changes in some of the unsaturated fatty acids (UFA) in the lipid fraction of these RBC membranes. Significant amounts of hexanal, heptanal, and nonanal are formed from the ozonation of UFA. Although no decrease in the amount of oleate is detected, it does undergo ozonation to yield nonanal; thus, as would be expected, product appearance is a more sensitive measure of ozonation than is substrate disappearance. These results imply that both proteins and unsaturated lipids undergo simultaneous and competitive ozonation in human RBC membranes when ozone is the limiting reactant. The ratios of reaction of ozone with different targets can be predicted in reasonably good agreement with the observed values using calculations (W. A. Pryor and R. M. Uppu (1993) J. Biol. Chem. 268, 3120-3126; R. M. Uppu and W. A. Pryor (1994) Chem. Res. Toxicol. 7, 47-55) that take into account the reactivities and relative amounts of protein and lipid functionalities present in the RBC membranes. Similar calculations are used to predict the reaction of ozone with unsaturated lipids and proteins at the air/lung interface, and both UFA and proteins are predicted to react with ozone in the lung, as in RBC membranes.
Uppu
R M
RM
Biodynamics Institute, Louisiana State University, Baton Rouge 70803-1800, USA.
Cueto
R
R
Squadrito
G L
GL
Pryor
W A
WA
D000110:Acetylcholinesterase / Q000097:blood; D000388:Air; D000447:Aldehydes / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D008563:Membrane Lipids / Q000097:blood; D008565:Membrane Proteins / Q000097:blood; D008954:Models, Biological; D010126:Ozone / Q000009:adverse effects* / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism
D000447:Aldehydes; D005231:Fatty Acids, Unsaturated; D008563:Membrane Lipids; D008565:Membrane Proteins; D013438:Sulfhydryl Compounds; D010126:Ozone; D000110:Acetylcholinesterase