Protective effects of mitochondria-targeted antioxidant SkQ in aqueous and lipid membrane environments.
The antioxidant activity of mitochondria-targeted small molecules, SkQ1 and MitoQ (conjugates of a lipophilic decyltriphenylphosphonium cation with an antioxidant moiety of a plastoquinone and ubiquinone, respectively), was studied in aqueous solution and in a lipid environment, i.e., micelles, liposomes and planar bilayer lipid membranes. Reactive oxygen species (ROS) were generated by azo initiators or ferrous ions with or without tert-butyl-hydroperoxide (t-BOOH). Chemiluminescence, fluorescence, oxygen consumption and inactivation of gramicidin peptide channels were measured to detect antioxidant activity. In all of the systems studied, SkQ1 was shown to effectively scavenge ROS. The scavenging was inherent to the reduced form of the quinone (SkQ1H(2)). In the majority of the above model systems, SkQ1 exhibited higher antioxidant activity than MitoQ. It is concluded that SkQ1H(2) operates as a ROS scavenger in both aqueous and lipid environments, being effective at preventing ROS-induced damage to membrane lipids as well as membrane-embedded peptides.
Antonenko
Y N
YN
A. N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, 119991, Moscow, Russian Federation. antonen@genebee.msu.ru
Roginsky
V A
VA
Pashkovskaya
A A
AA
Rokitskaya
T I
TI
Kotova
E A
EA
Zaspa
A A
AA
Chernyak
B V
BV
Skulachev
V P
VP
D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D002412:Cations; D016503:Drug Delivery Systems; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology*; D006096:Gramicidin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008081:Liposomes; D008823:Micelles; D051336:Mitochondrial Membranes / Q000737:chemistry / Q000187:drug effects*; D008954:Models, Biological; D009861:Onium Compounds / Q000737:chemistry / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000494:pharmacology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000378:metabolism; D010971:Plastoquinone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D014867:Water / Q000737:chemistry / Q000378:metabolism*
C532038:10-(6'-plastoquinonyl)decyltriphenylphosphonium; D000975:Antioxidants; D002412:Cations; D016166:Free Radical Scavengers; D008051:Lipid Bilayers; D008081:Liposomes; D008823:Micelles; D009861:Onium Compounds; D009943:Organophosphorus Compounds; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D014867:Water; D014451:Ubiquinone; D006096:Gramicidin; C429014:mitoquinone; D010971:Plastoquinone