title: Effects of Al(3+) and related metals on membrane phase state and hydration: correlation with lipid oxidation.
abstract: The aim of the present study was to further understand how changes in membrane organization can lead to higher rates of lipid oxidation. We previously demonstrated that Al(3+), Sc(3+), Ga(3+), Be(2+), Y(3+), and La(3+) promote lipid packing and lateral phase separation. Using the probe Laurdan, we evaluated in liposomes if the higher rigidity of the membrane caused by Al(3+) can alter membrane phase state and/or hydration, and the relation of this effect to Al(3+)-stimulated lipid oxidation. In liposomes of dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylserine, Al(3+) (10-100 microM) induced phase coexistence and displacement of T(m). In contrast, in liposomes of brain phosphatidylcholine and brain phosphatidylserine, Al(3+) (10-200 microM) did not affect membrane phase state but increased Laurdan generalized polarization (GP = -0. 04 and 0.09 in the absence and presence of 200 microM Al(3+), respectively). Sc(3+), Ga(3+), Be(2+), Y(3+), and La(3+) also increased GP values, with an effect equivalent to a decrease in membrane temperature between 10 and 20 degrees C. GP values in the presence of the cations were significantly correlated (r(2) = 0.98, P < 0.001) with their capacity to stimulate Fe(2+)-initiated lipid oxidation. Metal-promoted membrane dehydration did not correlate with ability to enhance lipid oxidation, indicating that dehydration of the phospholipid polar headgroup is not a mechanism involved in cation-mediated enhancement of Fe(2+)-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.
authors.affiliation: Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, Buenos Aires, 1113-, Argentina.
authors.forename: S V
authors.initials: SV
authors.lastname: Verstraeten
authors.forename: P I
authors.initials: PI
authors.lastname: Oteiza
mesh_terms: D015081:2-Naphthylamine / Q000031:analogs & derivatives / Q000378:metabolism; D000535:Aluminum / Q000378:metabolism / Q000494:pharmacology*; D001921:Brain; D002412:Cations / Q000378:metabolism / Q000494:pharmacology; D003460:Crystallization; D005456:Fluorescent Dyes / Q000378:metabolism; D007700:Kinetics; D007848:Laurates / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D008670:Metals / Q000378:metabolism / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D010713:Phosphatidylcholines / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013696:Temperature; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014867:Water / Q000378:metabolism*
chemical_list: D002412:Cations; D005456:Fluorescent Dyes; D007848:Laurates; D008081:Liposomes; D008670:Metals; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D010743:Phospholipids; D017392:Thiobarbituric Acid Reactive Substances; D014867:Water; C042859:dimyristoylphosphatidylserine; D015081:2-Naphthylamine; D000535:Aluminum; C065580:laurdan