Kynurenic acid attenuates MPP+-induced dopaminergic neuronal cell death via a Bax-mediated mitochondrial pathway

被引：63

作者：

Lee, Do Yeon ^{[1
,2
]}

Lee, Kyu-Sun ^{[3
]}

Lee, Hyun Jung ^{[1
]}

Noh, Yoo Hun ^{[1
]}

Kim, Do Hee ^{[1
]}

Lee, Jun Young ^{[4
]}

Cho, Soo Hyun ^{[5
]}

Yoon, Ok Ja ^{[6
]}

Lee, Won Bok ^{[1
]}

Kim, Kyung Yong ^{[1
]}

Chung, Yoon Hee ^{[1
]}

Kim, Sung Su ^{[1
]}

机构：

[1] Chung Ang Univ, Dept Anat & Cell Biol, Coll Med, Dongjak Ku, Seoul 156756, South Korea

[2] Korea Inst Oriental Med, Dept Herbal Resources Res, Taejon, South Korea

[3] Korea Res Inst Biosci & Biotechnol KRIBB, Ctr Regenerat Med, Taejon, South Korea

[4] Seoul Natl Univ, Coll Med, Dept Neuropsychiat, Seoul, South Korea

[5] Chung Ang Univ, Coll Med, Dept Family Med, Seoul 156756, South Korea

[6] Sungkyunkwan Univ, Sch Adv Mat Sci & Engn, Suwon, South Korea

来源：

EUROPEAN JOURNAL OF CELL BIOLOGY | 2008年 / 87卷 / 06期

关键词：

kynurenic acid (KYNA); 1-methyl-4-phenylpyridinium (MPP+); Bax; mitochondrial dysfunction; neuronal apoptosis;

D O I：

10.1016/j.ejcb.2008.03.003

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 [细胞生物学]; 090102 [作物遗传育种];

摘要：

Kynurenic acid (KYNA), a tryptophan metabolite in the kynurenine pathway, is protective against various insults. However, the molecular mechanism of this protective effect has not been identified. In this study, we examined the protective effects of KYNA against 1-methyl-4-phenylpyridinium (MPP+), the best-characterized toxin inducing pathological changes resembling Parkinson's disease (PD), using SH-SY5Y and SK-N-SH human neuroblastoma cells. Pre-treatment of KYNA attenuated MPP+-induced neuronal cell death in SH-SY5Y and SK-N-SH cells. MPP+-induced cell death was preceded by increases in Bax expression and mitochondrial dysfunction, such as collapse of mitochondrial membrane potential (Delta Psi(m)), release of cytochrome c from mitochondria into the cytoplasm, and increases in caspase-9/-3 activities. KYNA effectively inhibited all of these mitochondrial apoptotic processes. Our results indicate that KYNA plays a protective role by down-regulating Bax expression and maintaining mitochondrial function in MPP+-induced neuronal cell death, and suggest that KYNA may have therapeutic potential in PD. (C) 2008 Elsevier GmbH. All rights reserved.

引用

页码：389 / 397

页数：9

共 37 条

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