دورية أكاديمية

Potential cytotoxic effect of hydroxypyruvate produced from d-serine by astroglial d-amino acid oxidase.

التفاصيل البيبلوغرافية
العنوان: Potential cytotoxic effect of hydroxypyruvate produced from d-serine by astroglial d-amino acid oxidase.
المؤلفون: Seong Pil Chung, Sogabe, Kimiko, Hwan Ki Park, Ying Song, Ono, Koji, Abou El-Magd, Rabab M., Shishido, Yuji, Yorita, Kazuko, Sakai, Takashi, Fukui, Kiyoshi
المصدر: Journal of Biochemistry; Dec2010, Vol. 148 Issue 6, p743-753, 11p, 1 Diagram, 2 Charts, 9 Graphs
مصطلحات موضوعية: AMINO acids, OXIDATIVE stress, FLAVOPROTEINS, HYDROGEN peroxide, AMMONIA, MAMMALS
مستخلص: 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 α-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 the metabolism 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 activity in astroglial cell. Furthermore, this cytotoxicity of HPA is observed uniquely in astroglial cells expressing DAO. [ABSTRACT FROM PUBLISHER]
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قاعدة البيانات: Complementary Index
الوصف
تدمد:0021924X
DOI:10.1093/jb/mvq112