Impact of oxidized lipids and antioxidants, such as vitamin E and lazaroids, on the structure and dynamics of unsaturated membranes
The structural and dynamic effects of well defined, synthesized lipid peroxidation products (PLPC-OH and PLPC-OOH), the natural membrane-bound antioxidant vitamin E (α-tocopherol and β-tocopherol) and three synthetic membrane-bound antioxidants (the lazaroids U-74006F, U-75412 and U78518E) on bilayer lipid membranes have been investigated by time-resolved fluorescence depolarization and angle-resolved fluorescence depolarization (AFD) techniques and by electron paramagnetic resonance utilizing probe molecules. The lipid peroxidation products strongly disorder the investigated unsaturated lipid membranes, but they do not affect the lipid dynamics. The disordering effect is compatible with a model where the lipid hydroperoxy of hydroxy moieties reside closer to the polar head-group region of the membrane lipids. Fluorescence depolarization data obtained from the intrinsic fluorescence of α-tocopherol indicate that the trolox moiety of α-tocopherol (the fluorophore and antioxidant part of the molecule) can have different orientations in DOPC membranes depending on the α-tocopherol concentration. These orientational possibilities and the location of the lipid hydroperoxy moieties in lipid bilayers may account for the high reaction efficiency of α-tocopherol with lipid hydroperoxy radicals in membranes. Vitamin E in low and in high concentrations does not affect the molecular orientational order in membranes, but it does affect the dynamics. Because of the lack of structural effects of vitamin E on unsaturated lipid membranes without or with lipid peroxidation products, the hypothesis of vitamin E functioning as a membrane-stabilizing agent is questionable.
In contrast with vitamin E, the three lazaroids as synthetic antioxidants have different effects on membrane structure and dynamics. The steroid-based lazaroids U-74006F and U-75412 have a disordering effect in the majority of the lipid systems investigated whereas the effects on dynamics vary depending on the surrounding lipids. The trolox derivative U-78518E, structurally closely related to α-tocopherol, has no or small ordering effects while the effects on dynamics also vary depending on the surrounding lipids. The effects of the different compounds on the molecular orientational order of membranes may be understood by their overall molecular shape. The main question that as yet remains unanswered is: which factors determine the dynamic effects of molecules in membranes?