LIPID-PEROXIDATION OF THE BRUSH-BORDER MEMBRANE - MEMBRANE PHYSICAL-PROPERTIES AND GLUCOSE-TRANSPORT

During inflammatory conditions, peroxidation of biological membranes o ften takes place. Deleterious physiological consequences, in terms of membrane function, could theoretically be mediated by either direct ox idative attack upon integral membrane proteins or by indirectly alteri ng the lipid environment surrounding these proteins. To address this i ssue, in vitro peroxidation of guinea pig brush-border membrane vesicl es was induced by incubation of the vesicles with ferrous sulfate and ascorbic acid. We found that ongoing peroxidative attack initiates lip id peroxidation and radically alters the physical properties of the me mbrane lipid bilayer in a well-defined and regional manner. Peroxidati on of microvillous membrane produced an increasingly rigid membrane. C oupled with these alterations was a fivefold reduction in maximal rate s of sodium-dependent glucose transport that appeared to have a multif actorial origin. Approximately one-third of this reduction was seconda ry to altered membrane physical properties and was reversible by fluid izing the vesicles and returning membrane physical properties to norma l. The remaining reduction in glucose transport activity was not respo nsive to membrane fluidization and was presumably related to direct da mage of the transport protein.