Sc3+, Ga3+, In3+, Y3+, and Be2+ Promote Changes in Membrane Physical Properties and Facilitate Fe2+-Initiated Lipid Peroxidation

The capacity of metals chemically and physically related to Al (Sc, Ga, In, Y, and Be) to promote liposome aggregation, fusion, and permeabilization and to stimulate Fe2+-initiated lipid peroxidation was investigated in negatively charged liposomes. The effects of Sc, Ga, In, Be, and Y were compared with those of trivalent (Al, La) and divalent cations. At 50 μM concentration, Al, Sc, Ga, In, Y, and La released 5(6)-carboxyfluorescein from liposomes and the magnitude of the effect was Al, In > Ga, Sc > La, Y. At concentrations between 10 and 200 μM, Sc, Ga, In, Y, and Be caused liposome aggregation and fusion. Al, Sc, Ga, In, and Be had their maximal effect on liposome fusion and aggregation at 100 μM; Y and La had their maximal effect at 20 μM. Metal-induced fusion was dependent on the negative charge density of the liposomes. Sc, Ga, In, Be, and Y stimulated Fe2+-initiated lipid peroxidation in a time- and dose-dependent manner. The fusogenic capacity of these nonredox metals was positively correlated with their capacity to induce Fe2+-supported lipid peroxidation. Results suggest that metals without redox capacity can promote lipid peroxidation, in the presence of an initiator of the oxidative chain, by affecting membrane physical properties.