Effects of Al3+ and related metals on membrane phase state and hydration: Correlation with lipid oxidation

The aim of the present study was to further understand how changes in membr ane organization can lead to higher rates of lipid oxidation. We previously demonstrated that Al3+, SC3+, (Ga3+) Be2+, Y3+, and La3+ promote lipid pac king and lateral phase separation. Using the probe Laurdan, we evaluated in liposomes if the higher rigidity of the membrane caused by Al3+ can alter membrane phase state and/or hydration, and the relation of this effect to A l3+-stimulated lipid oxidation. In liposomes of dimyristoyl phosphatidylcho line and dimyristoyl phosphatidylserine, Al3+ (10-100 mu M) induced phase c oexistence and displacement of T-m. In contrast, in liposomes of brain phos phatidylcholine and brain phosphatidylserine, Al3+ (10-200 mu M) did not af fect membrane phase state but increased Laurdan generalized polarization (G P = -0.04 and 0.09 in the absence and presence of 200 mu M Al3+, respective ly). Sc3+, Ga3+, Be2+, Y3+, and La3+ also increased GP values, with an effe ct equivalent to a decrease in membrane temperature between 10 and 20 degre es C. GP values in the presence of the cations were significantly correlate d (r(2) = 0.981 P < 0.001) With their capacity to stimulate Fe2+-initiated lipid oxidation. Metal-promoted membrane dehydration did not correlate with ability to enhance lipid oxidation, indicating that dehydration of the pho spholipid polar headgroup is not a mechanism involved in cation-mediated en hancement of Fe2+-initiated lipid oxidation. Results indicate that changes in membrane phospholipid phase state favoring the displacement to gel state can facilitate the propagation of lipid oxidation. (C) 2000 Academic Press .