Functional Modification of Cytochrome c by Peroxynitrite in an Electron Transfer Reaction
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概要
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The redox reaction of cytochrome c after modification with peroxynitrite under physiological conditions was investigated. Cytochrome c was treated with a bolus of synthetic peroxynitrite at a sub-millimolar concentration, and then subjected to reduction by superoxide and oxidation by hydrogen peroxide. The ability for the membrane potential formation in the mitochondrial respiratory chain was also evaluated. After the treatment with peroxynitrite, the cytochrome c molecule was mono-nitrated mainly at a tyrosine residue, using liquid chromatography-electrospray ionizing mass spectrometry(LC-ESI-MS) and HPLC. Although the redox capacity of cytochrome c was not affected by the peroxynitrite treatment, the oxidation of ferrocytochrome c to ferricytochrome c by hydrogen peroxide was accelerated. When cytochrome c was treated with peroxynitrite in the presence of 5-methoxytryptamine, an inhibitor for the tyrosine nitration by peroxynitrite, the acceleration of hydrogen peroxide-mediated oxidation was suppressed. It was also found that the formation of membrane potential in the rat liver mitochondria was suppressed when peroxynitrite-treated cytochrome c was used instead of the intact cytochrome c in vitro. From these results, we concluded that the peroxynitrite-treated cytochrome c was nitrated at a tyrosine residue and became more susceptible to oxidation by hydrogen peroxide, concomitantly losing the ability to transfer electrons in the mitochondrial respiratory chain. It is suggested that the peroxynitrite-induced modification of cytochrome c increases the susceptibility to non-physiological oxidants, and may cause dysfunction of mitochondria by suppressing of membrane potential.
- 公益社団法人日本薬学会の論文
- 2001-12-01
著者
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伊古田 暢夫
放射線医学総合研究所
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清水 栄
Faculty of Pharmaceutical Sciences, Kanazawa University
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伊古田 暢夫
放射線医学総合研究所重粒子医科学センター
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OZAWA Toshihiko
Department of Health Pharmacy, Yokohama College of Pharmacy
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Ikota Nobuo
Research Center For Radiation Emergency Medicine National Institute Of Radiological Sciences
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IKOTA Nobuo
Bioreguration Research Group, National Institute of Radiological Sciences
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Shimizu Shigeomi
Biomedical Research Center Osaka University School Of Medicine
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Ikota Nobuo
Redox Regulation Research Group National Institute Of Radiological Sciences
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TAKUSAGAWA Mitsuko
Redox Regulation Research Group, National Institute of Radiological Sciences
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NAKAGAWA Hidehiko
Bioregulation Research Group, National Institute of Radiological Sciences
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OHSHIMA Yukiko
Bioregulation Research Group, National Institute of Radiological Sciences
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TAKUSAGAWA Mitsuko
Bioregulation Research Group, National Institute of Radiological Sciences
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TAKAHASHI Yutaka
Analytical Instruments Division, JEOL Ltd.
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OZAWA Toshihiko
Bioregulaiton Research Group, National Institute of Radiological Sciences
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Ozawa Toshihiko
Radiation Modifier Research Team Heavy-ion Radiobiology Research Group Research Center For Charged P
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Nakagawa Hidetoshi
Faculty Of Pharmaceutical Sciences Kumamoto University
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Takahashi Y
Analytical Instruments Division Jeol Ltd.
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Ozawa Toshihiko
放射線医学総合研究所重粒子医科学センター 粒子線生物研究グループ
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Ohshima Y
Bioregulation Research Group National Institute Of Radiological Sciences
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Nakagawa H
Mukogawa Women's Univ. Nishinomiya Jpn
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Nakagawa Hiroshi
Graduate School Of Pharmaceutical Sciences The University Of Tokyo
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Nakagawa Hidehiko
Department Of Organic And Medicinal Chemistry Graduate School Of Pharmaceutical Sciences Nagoya City
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Takahashi Yutaka
Analytical Instrument Division Jeol Ltd.
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Takusagawa Mitsuko
Redox Regulation Research Group National Institute Of Radiological Sciences
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