Mechanisms of stabilization of biomembranes by alpha-tocopherol. The role of the hydrocarbon chain in the inhibition of lipid peroxidation.
The effects of alpha-tocopherol and its homologues with different chain lengths (6-hydroxy-chromanes: C1, C6, C11) on lipid peroxidation in natural membranes (liver microsomes and mitochondria, brain synaptosomes) and liposomes were studied. It was shown that the antioxidant activity of alpha-tocopherol homologues decreased in the order: C1 greater than C6 greater than C11 greater than alpha-tocopherol (C16). Using fluorescent measurements, the possible reasons underlying these differences were investigated: (i) the distribution between the aqueous media and nonpolar phase of the membrane, which predetermines the binding of alpha-tocopherol homologues to membranes; (ii) the incorporation of alpha-tocopherol homologues into lipid bilayer; (iii) non-uniform distribution (formation of the clusters) of tocopherol homologues in the lipid bilayer; and (iv) transbilayer mobility of alpha-tocopherol homologues and accessibility of the inhibitors for radical-generating centres under enzymically and non-enzymically induced lipid peroxidation. It was demonstrated that: (i) binding of C1 with membranes was less efficient than that of longer-chain homologues (C6, C11, C16); (ii) the level of incorporation of alpha-tocopherol homologues into membranes decreased in a succession alpha-tocopherol C11 greater than C6 greater than C1; (iii) all alpha-tocopherol homologues existed in the lipid bilayer not only in a monomeric form but also associated in clusters thus decreasing the efficiency of radical scavenging; (iv) the short-chain alpha-tocopherol homologue, C1, exhibited a high transbilayer mobility whereas the long-chain one, C16, underwent no transbilayer migration within tens of minutes. The inhibiting effect of alpha-tocopherol esters and C1-acetate was predetermined by their hydrolysis in biomembranes; a strong correlation exists between the rate of the ester hydrolysis and their antioxidant activity in the membrane. In liposomes, in which the esterase activity was absent, alpha-tocopherol esters and C1-acetate exhibited very low lipid peroxidation inhibition.
Kagan
V E
VE
Institute of Physiology, Bulgarian Academy of Science, Sofia.
Serbinova
E A
EA
Bakalova
R A
RA
Stoytchev
T S
TS
Erin
A N
AN
Prilipko
L L
LL
Evstigneeva
R P
RP
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects*; D008051:Lipid Bilayers / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism / Q000494:pharmacology*
D008051:Lipid Bilayers; D014810:Vitamin E