RESEARCH PAPER

AGING, Vol 1, No 5 , pp 481-489
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Chain-breaking antioxidant activity of reduced forms of mitochondria-targeted quinones, a novel type of geroprotectors

Vitaly A. Roginsky1,2, Vadim N. Tashlitsky2,3,, Vladimir P. Skulachev2,4
1N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, 119991 Moscow, Russian Federation
2 Center of Mitoengineering, Moscow State University, 119991, Moscow, Russian Federation
3 Chemical Department, Moscow State University, 119991 Moscow, Russian Federation
4 A.N.Belozersky Institute of Physico-Chemical Biology, Moscow State University, 119991 Moscow, Russian Federation
Running title:
Chain-breaking activity of geroprotectors
Key words:
Geroprotector; mitochondria-targeted antioxidants; plastoquinone; ubiquinone; antioxidant activity; triphenylphosphonium
Received:
03/06/09; accepted: 05/11/09; published on line: 05/12/09
Correspondence:
E-mail:

Abstract

The chain-breaking antioxidant activities of reduced form of novel type of geroprotectors, mitochondria-targeted quinones (QH2) have quantitatively been measured for the first time. To this end, the chain peroxidation of methyl linoleate (ML) in Triton micelles was used as a kinetic testing model. The studied QH2 were lipophilic triphenylphosphonium cations conjugated by an aliphatic linker to an antioxidant, i.e. a ubiquinol moiety (MitoQH2) or plastoquinol moiety (SkQH2). The antioxidant activity was characterized by the rate constant k1 for the reaction between QH2 and the lipid peroxyl radical (LO2•) originated from ML: QH2 + LO2• HQ• + LOOH. All the tested QH2 displayed a pronounced antioxidant activity. The oxidized forms of the same compounds did not inhibit ML peroxidation. The value of k1 for SkQH2 far exceeded k1 for MitoQH2. For the biologically active geroprotectors SkQ1H2, the k1 value found to be as high as 2.2 x 105 M-1s-1, whereas for MitoQH2, it was 0.58 x 105 M-1s-1. The kinetic behavior of QH2 suggested that SkQ1H2 can rather easily diffuse through lipid-water microheterogeneous systems.

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