Nitration of Specific Tyrosine Residues of Cytochrome c Is Associated with Caspase-Cascade Inactivation
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- Nakagawa Hidehiko
- Department of Organic and Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University
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- Komai Nobuko
- 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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- Miura Yuri
- Tokyo Metropolitan Institute of Gerontology
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- Toda Tosifusa
- Tokyo Metropolitan Institute of Gerontology
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- Miyata Naoki
- Department of Organic and Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University
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- Ozawa Toshihiko
- Redox Regulation Research Group, National Institute of Radiological Sciences
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- Ikota Nobuo
- Redox Regulation Research Group, National Institute of Radiological Sciences
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抄録
Peroxynitrite, a potent oxidative stress inducer, inhibits the mitochondrial electron transfer, induces cell death, and is considered to be involved in the pathology of various diseases. However, the intracellular mechanisms involved in the cell death process are not fully understood. Here we demonstrate that the enhanced nitration of specific tyrosine residues of cytochrome c, which are induced by continuous peroxynitrite exposure, attenuates cytochrome c-induced caspase-9 activation in vitro. Interestingly, cytochrome c nitrated with a single high dose of peroxynitrite preserved its potency, while this did not occur when cytochrome c was treated with continuous peroxynitrite exposure. Although both of these experiments resulted in cytochrome c nitration at the tyrosine residues, it was found that nitration at specific residues was enhanced only when cytochrome c was exposed to continuous peroxynitrite. This is the first report to demonstrate that cytochrome c nitration affects the apoptotic pathway by means of enhancement of nitration at specific tyrosine residues. This result implies that the nitration pattern of cytochrome c may affect the efficacy of the mitochondrial pathway in apoptotic cell death.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 30 (1), 15-20, 2007
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390282679603937024
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- NII論文ID
- 110006153259
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- NII書誌ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 8589900
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- CiNii Articles
- KAKEN
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- 使用不可