Lipid peroxidation of the brush-border membrane: membrane physical properties and glucose transport

During inflammatory conditions, peroxidation of biological membranes often takes place. Deleterious physiological consequences, in terms of membrane function, could theoretically be mediated by either direct oxidative attack upon integral membrane proteins or by indirectly altering the lipid environment surrounding these proteins. To address this issue, in vitro peroxidation of guinea pig brush-border membrane vesicles was induced by incubation of the vesicles with ferrous sulfate and ascorbic acid. We found that ongoing peroxidative attack initiates lipid peroxidation and radically alters the physical properties of the membrane lipid bilayer in a well-defined and regional manner. Peroxidation of microvillous membrane produced an increasingly rigid membrane. Coupled with these alterations was a fivefold reduction in maximal rates of sodium-dependent glucose transport that appeared to have a multifactorial origin. Approximately one-third of this reduction was secondary to altered membrane physical properties and was reversible by fluidizing the vesicles and returning membrane physical properties to normal. The remaining reduction in glucose transport activity was not responsive to membrane fluidization and was presumably related to direct damage of the transport protein.