TY - JOUR
T1 - Copper-induced peroxidation of phosphatidylserine-containing liposomes is inhibited by nanomolar concentrations of specific antioxidants
AU - Gal, S.
AU - Lichtenberg, D.
AU - Bor, A.
AU - Pinchuk, I.
N1 - Funding Information:
We acknowledge the Lady Davis chair of Biochemistry and Israel Science Foundation for financial support (research grant 362/02-18.1) and Prof. Vaya of the Migal Galilee Technology Center for helpful discussions and for his gift of 11 different flavonoids (products of ICC).
PY - 2007/12
Y1 - 2007/12
N2 - Copper-induced peroxidation of liposomal palmitoyllinoleoyl-phosphatidylcholine (PLPC) is inhibited by α-tocopherol at micromolar concentrations. In our previous study we found that when the liposomes contain phosphatidylserine (PS), nanomolar concentrations of Toc were sufficient to inhibit peroxidation. In an attempt to gain understanding of the origin of this extreme antioxidative potency, we tested the antioxidative potency of 36 additional antioxidants and the dependence of their potency on the presence of PS in the liposomes. The results of these studies reveal that only 11 of the tested antioxidants possess similar antioxidative potency to that of Toc. These include trolox, butylated hydroxytoluene (BHT), curcumin, nordihydroguaiaretic acid (NDGA), diethylstilbestrol (DES), 2 of the 13 tested flavonoids (luteolin and 7,3′,4′-trihydroxyflavone; T-414), α-naphthol, 1,5-, 1,6- and 1,7-dihydroxynaphthalenes (DHNs). Propyl gallate (PG), methyl syringate, rosmarinic acid, resveratrol, other flavonoids, as well as β-naphthol, 1,2-, 1,3-, 1,4-, 2,3-, 2,6-, and 2,7-DHNs were either moderately antioxidative or pro-oxidative. For liposomes made of PLPC (250 μM) and PS (25 μM) the "lag" preceding copper-induced peroxidation (5 μM copper) was doubled upon addition of 30-130 nM of the "super-active" antioxidants. We propose that the mechanism responsible for the extreme antioxidative potency against copper-induced peroxidation in PS-containing liposomes involves replenishment of the antioxidant in a ternary PS-copper-antioxidant complex. Based on structure-activity relationship of the 37 tested antioxidants, the "super-antioxidative potency" is attributed to the recycling of relatively stable semiquinone or semiquinone-like radicals.
AB - Copper-induced peroxidation of liposomal palmitoyllinoleoyl-phosphatidylcholine (PLPC) is inhibited by α-tocopherol at micromolar concentrations. In our previous study we found that when the liposomes contain phosphatidylserine (PS), nanomolar concentrations of Toc were sufficient to inhibit peroxidation. In an attempt to gain understanding of the origin of this extreme antioxidative potency, we tested the antioxidative potency of 36 additional antioxidants and the dependence of their potency on the presence of PS in the liposomes. The results of these studies reveal that only 11 of the tested antioxidants possess similar antioxidative potency to that of Toc. These include trolox, butylated hydroxytoluene (BHT), curcumin, nordihydroguaiaretic acid (NDGA), diethylstilbestrol (DES), 2 of the 13 tested flavonoids (luteolin and 7,3′,4′-trihydroxyflavone; T-414), α-naphthol, 1,5-, 1,6- and 1,7-dihydroxynaphthalenes (DHNs). Propyl gallate (PG), methyl syringate, rosmarinic acid, resveratrol, other flavonoids, as well as β-naphthol, 1,2-, 1,3-, 1,4-, 2,3-, 2,6-, and 2,7-DHNs were either moderately antioxidative or pro-oxidative. For liposomes made of PLPC (250 μM) and PS (25 μM) the "lag" preceding copper-induced peroxidation (5 μM copper) was doubled upon addition of 30-130 nM of the "super-active" antioxidants. We propose that the mechanism responsible for the extreme antioxidative potency against copper-induced peroxidation in PS-containing liposomes involves replenishment of the antioxidant in a ternary PS-copper-antioxidant complex. Based on structure-activity relationship of the 37 tested antioxidants, the "super-antioxidative potency" is attributed to the recycling of relatively stable semiquinone or semiquinone-like radicals.
KW - Copper-induced peroxidation
KW - Dihydroxynaphthalenes
KW - Flavonoids
KW - Liposomes
KW - Naphthols
KW - Phosphatidylserine
UR - http://www.scopus.com/inward/record.url?scp=35148822753&partnerID=8YFLogxK
U2 - 10.1016/j.chemphyslip.2007.08.001
DO - 10.1016/j.chemphyslip.2007.08.001
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AN - SCOPUS:35148822753
SN - 0009-3084
VL - 150
SP - 186
EP - 203
JO - Chemistry and Physics of Lipids
JF - Chemistry and Physics of Lipids
IS - 2
ER -