The applicant' s broad, long-term objectives are to understand the biochemical basis for toxicity of ozone to biological systems.
The specific aims of this project are to assay quantitatively the fraction of ozone reacting with protein and lipid components of the plasma membrane. The health relatedness of the project is that ozone is a prevalent air pollutant which has its effect on health by inhalation into the lungs. The ozone reacts with the cell types present in the alveolar sacs and respiratory bronchioles. The results expected in the current study will provide a better understanding of the initial reactions of ozone with sensitive cell types. The research of the first year will examine the reaction of ozone with human erythrocyte plasma membranes. After ozone exposure the lipid and proteins will be separated for analysis. The proteins will be examined for overall changes in amino acid composition, enzyme inhibition, and a detailed study will be made of the oxidation of susceptible amino acids in the Band III proteins (anion exchange protein). The latter analysis will show whether the only amino acids oxidized by ozone are extra-membranous. The lipid component will be examined for the type and quantity of phospholipids which have been modified by ozonolysis. These modified lipids behave distinctly when molecular species of phospholipids are analyzed. In the second and third years the reaction of ozone with cultured macrophage plasma membranes will be examined by the described techniques.
Mudd, J B; Dawson, P J; Santrock, J (1997) Ozone does not react with human erythrocyte membrane lipids. Arch Biochem Biophys 341:251-8 |
Mudd, J B; Dawson, P J; Adams, J R et al. (1996) Reaction of ozone with enzymes of erythrocyte membranes. Arch Biochem Biophys 335:145-51 |