Monoamine-dependent Production of Reactive Oxygen Species Catalyzed by Pseudoperoxidase Activity of Human Hemoglobin(Biochemistry & Molecular Biology)
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概要
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Hemoglobin (Hb) solution-based blood substitutes are being developed as oxygen-carrying agents for the prevention of ischemic tissue damage and low blood volume-shock. However, the cell-free Hb molecule has intrinsic toxicity to the tissue since harmful reactive oxygen species (ROS) are readily produced during autoxidation of Hb from the ferrous state to the ferric state, and the cell-free Hb also causes distortion in the oxidant/antioxidant balance in the tissues. There may be further hindering dangers in the use of free Hb as a blood substitute. It has been reported that Hb has peroxidase-like activity oxidizing peroxidase substrates such as aromatic amines. Here we observed the Hb-catalyzed ROS production coupled to oxidation of a neurotransmitter precursor, β-phenylethylamine (PEA). Addition of PEA to Hb solution resulted in generation of superoxide anion (O^<・->_2). We also observed that PEA increases the Hb-catalyzed monovalent oxidation of ascorbate to ascorbate free radicals (Asc^・). The O^<・->_2 generation and Asc^・ formation were detected by O^<・->_2-specific chemiluminescence of the Cypridina lucigenin analog and electron spin resonance spectroscopy, respectively. PEA-dependent O^<・->_2 production and monovalent oxidation of ascorbate in the Hb solution occurred without addition of H_2O_2, but a trace of H_2O_2 added to the system greatly increased the production of both O^<・->_2 and Asc^・. Addition of GSH completely inhibited the PEA-dependent production of O^<・->_2 and Asc^・ in Hb solution. We propose that the O^<・->_2 generation and Asc^・ formation in the Hb solution are due to the pseudoperoxidase activity-dependent oxidation of PEA and resultant ROS may damage tissues rich in monoamines, if the Hb-based blood substitutes were circulated without addition of ROS scavengers such as thiols.
- 社団法人日本農芸化学会の論文
- 2002-06-23
著者
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KAWANO Tomonori
Department of Cardiology and Cardiovascular Surgery, Shinkyo Hospital
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PINONTOAN Reinhard
Nagoya University Bioscience Center, Nagoya University
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Kawano Tomonori
Fac. And Graduate School Of Environmental Engineering The Univ. Of Kitakyushu
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HOSOYA Hishoshi
Department of Biological Science, Graduate School of Science, Hiroshima University
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MUTO Sshoshi
Nagoya University Bioscience Center, Nagoya University
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Pinontoan Reinhard
Nagoya University Bioscience Center Nagoya University
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Pinontoan Reinhard
Nagoya University Bioscience Center
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Muto Sshoshi
Nagoya University Bioscience Center Nagoya University
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Hosoya Hishoshi
Department Of Biological Science Graduate School Of Science Hiroshima University
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Kawano Tomonori
Department of Biological and Environmental Chemistry, Faculty of Agriculture, Tottori University
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