TAILIEUCHUNG - Báo cáo khoa học: A selenium-containing single-chain abzyme with potent antioxidant activity

Reactive oxygen species (ROS) are products of normal metabolic activities and are thought to be the cause of many diseases. A selenium-containing single-chain abzyme 2F3 (Se-2F3-scFv) that imitates glutathione peroxidase has been produced which has the capacity to remove ROS. To evaluate the antioxidant ability of Se-2F3-scFv, we con-structeda ferrous sulfate/ascorbate (Vc/Fe 2+ )-inducedmito-chondrial damage model system and investigated the capacity of Se-2F3-scFv to protect mitochondria from oxi-dative damage. Se-2F3-scFv markedly decreased mito-chondrial swelling, inhibited lipid peroxidation, and maintained the activity of cytochromecoxidase, in com-parison with Ebselen, a well-studied glutathione peroxidase mimic, indicating that Se-2F3-scFvhas potential for treating diseases mediated by ROS | Eur. J. Biochem. 270 4326-4331 2003 FEBS 2003 doi A selenium-containing single-chain abzyme with potent antioxidant activity Delin You1 Xiaojun Ren1 2 Yan Xue1 Guimin Luo1 Tongshu Yang1 and Jiacong Shen2 1Key Laboratory of Molecular Enzymology and Engineering of Ministry of Education Jilin University Changchun P. R. China 2Key Laboratory for Supramolecular Structure and Materials of Ministry of Education Jilin University Changchun P. R. China Reactive oxygen species ROS are products of normal metabolic activities and are thought to be the cause of many diseases. A selenium-containing single-chain abzyme 2F3 Se-2F3-scFv that imitates glutathione peroxidase has been produced which has the capacity to remove ROS. To evaluate the antioxidant ability of Se-2F3-scFv we constructed a ferrous sulfate ascorbate Vc Fe2 -induced mitochondrial damage model system and investigated the capacity of Se-2F3-scFv to protect mitochondria from oxi dative damage. Se-2F3-scFv markedly decreased mitochondrial swelling inhibited lipid peroxidation and maintained the activity of cytochrome c oxidase in comparison with Ebselen a well-studied glutathione peroxidase mimic indicating that Se-2F3-scFv has potential for treating diseases mediated by ROS. Keywords antioxidant activity glutathione peroxidase mitochondria scFv selenium. Reactive oxygen species ROS include free radicals such as superoxide anion O2 and hydroxyl radical OH as well as nonradical intermediates such as hydrogen peroxide H2O2 hydroperoxide ROOH nitric oxide NO and singlet oxygen 1O2 1 2 . All these ROS are produced from molecular oxygen by mitochondrial electron carriers and from enzymes during normal metabolism of oxidative phosphorylation of aerobic mammalian cells. In addition ROS are produced on irradiation both ionizing and UV irradiation. To protect themselves from oxidative injury aerobic cells have evolved an enzymatic and nonenzymatic defense system. The enzymatic antioxidant .

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