LIPID-PEROXIDATION CONTRIBUTES TO AGE-RELATED MEMBRANE RIGIDITY

The aim of this work was to assess the relative contributions of lipid peroxidation and cholesterol content to the increase in membrane rigi dity observed during senescence. Membrane fluidity was manipulated thr ough exposure to peroxidized or cholesterol-loaded liposomes. Small un ilamella liposomes were prepared and either peroxidized by Fe++-ADP-as corbic acid or loaded with cholesterol. After incorporation of the lip osomes into rat liver microsomal membranes, membrane fluidity was quan titated by measuring changes in polarization. Membranes exhibited a gr eater sensitivity to peroxidation than cholesterol in that incorporati on of peroxidized liposomes induced microsomal membrane rigidity subst antially more than did cholesterol-loaded liposomes. Thus it is propos ed, based on data from the present and earlier studies, that membrane fluidity can be modulated readily by lipid peroxidation of membrane ph ospholipids, irrespective of the influences of cholesterol. These resu lts support the proposal that alterations of lipid structure are more potent and effective than compositional changes in cholesterol in indu cing age-related increases in membrane rigidity.