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オノ コウジ
ONO Koji
小野 公嗣 所属 埼玉医科大学 保健医療学部 臨床検査学科 職種 准教授 |
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| 論文種別 | 学術雑誌(原著) |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | Potential cytotoxic effect of hydroxypyruvate produced from d-serine by astroglial d-amino acid oxidase |
| 掲載誌名 | 正式名：JOURNAL OF BIOCHEMISTRY ISSNコード：0021924X |
| 出版社 | OXFORD UNIV PRESS |
| 巻・号・頁 | 148(6),743-753頁 |
| 著者・共著者 | Seong Pil Chung,Kimiko Sogabe,Hwan Ki Park,Ying Song,Koji Ono,Rabab M. Abou El-Magd,Yuji Shishido,Kazuko Yorita,Takashi Sakai,Kiyoshi Fukui |
| 発行年月 | 2010/12 |
| 概要 | d-Amino acid oxidase (DAO) is a flavoenzyme that exists in the kidney, liver and brain of mammals. This enzyme catalyzes the oxidation of d-amino acids to the corresponding alpha-keto acid, hydrogen peroxide and ammonia. Recently d-serine, one of the substrates of DAO, has been found in the mammalian brain, and shown to be a co-agonist of the N-methyl-d-aspartate (NMDA) receptor in glutamate neurotransmission. In this study, we investigated themetabolism of extracellular d-serine and the effects of d-serine metabolites to study the pathophysiological role of DAO. Treatment with a high dose of d-serine induced the cell death in dose-dependent manner in DAO-expressing cells. Moreover, overexpression of DAO in astroglial cells induced the enhanced cytotoxicity. The treatment with 1 mM beta-hydroxypyruvate (HPA), uniquely produced from the d-serine metabolism by DAO activity, also induced cell death, comprising apoptosis, in the astroglial cell, but not in the other cells derived from liver and kidney. Taken together, we consider that high dose of extracellular d-serine induced cell death by the production of not only hydrogen peroxide but also HPA as a result of DAO catalytic activit |
| DOI | 10.1093/jb/mvq112 |