Aldose reductase deficiency leads to oxidative stress-induced dopaminergic neuronal loss and autophagic abnormality in an animal model of Parkinson's disease

doi:10.1016/j.neurobiolaging.2016.11.008

科研成果详情

题名	Aldose reductase deficiency leads to oxidative stress-induced dopaminergic neuronal loss and autophagic abnormality in an animal model of Parkinson's disease
作者	Yeung，Patrick K.K.1; Lai，Angela K.W.1; Son，Hyo Jin 2; Zhang，Xu 1; Hwang，Onyou 2; Chung，Stephen S.M.3; Chung，Sookja K.1,4
发表日期	2017-02-01
发表期刊	Neurobiology of Aging
ISSN/eISSN	0197-4580
卷号	50 页码:119-133
摘要	Fungicide exposure causes degeneration of dopaminergic neurons and contributes to Parkinson's disease (PD). Benomyl inhibits enzymes responsible for detoxifying the reactive dopamine metabolite 3,4-dihydroxyphenylacetaldehyde. Aldose reductase (AR) is known as tetrahydrobiopterin (BH) reductase that generates BH, a cofactor for tyrosine hydroxylase (TH) involved in dopamine synthesis. AR also acts as an aldehyde reductase involved in detoxifying 3,4-dihydroxyphenylacetaldehyde. In PD patients, the level of AR is significantly lower in the cerebellum. To determine if AR deficiency contributes to PD, AR wild-type (AR) and knockout (AR) mice were administrated with 1-methyl-4-phenyl -1,2,3,6- tetrahydropyridine (MPTP). The MPTP-treated AR mice showed more severe behavioral deficits and brain damage than that of AR mice. Contrary to expectation, under normal or MPTP-treated condition, AR mice showed a significant elevation of BH and dopamine in the midbrain, suggesting that either AR does not contribute to BH production, or other BH synthetic pathways are induced. The AR brain showed upregulation of peroxynitrite, inducible nitric oxide synthase and downregulation of antioxidant enzymes, Cu/Zn superoxide dismutase (SOD) and peroxiredoxin 2 (Prx2), which indicate an increase in oxidative stress. In line with the animal data, pretreating the SH-SY5Y cells with AR inhibitors (Fidarestat or Epalrestat) before MPP treatment, increased severe cell death and mitochondrial fragmentation with downregulation of SOD were observed when compared to the MPP treatment alone. Cycloxygenase 2 (COX2), which can lead to the oxidation of dopamine, was upregulated in AR brains. Autophagic proteins, beclin-1 and LC3B were also downregulated. The loss of dopaminergic neurons was associated with activation of p-ERK1/2. These findings suggest that AR plays an important role in protecting dopaminergic neuron against neurotoxic metabolites in PD.
关键词	Aldose reductase Knockout mice Oxidative stress Parkinson's disease
DOI	10.1016/j.neurobiolaging.2016.11.008
URL	查看来源
语种	英语English
Scopus入藏号	2-s2.0-85002665130
引用统计	被引频次：23[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://repository.uic.edu.cn/handle/39GCC9TT/6370
专题	北师香港浸会大学
通讯作者	Chung，Sookja K.
作者单位	1.School of Biomedical Sciences,The University of Hong Kong,Hong Kong SAR,Hong Kong 2.Department of Biochemistry,University of Ulsan College of Medicine,Seoul,South Korea 3.Division of Science and Technology,United International College,Zhuhai,China 4.Research Center of Heart,Brain,Hormone and Healthy Aging,Li Ka Shing Faculty of Medicine,The University of Hong Kong,Hong Kong SAR,China
推荐引用方式 GB/T 7714	Yeung，Patrick K.K.,Lai，Angela K.W.,Son，Hyo Jinet al. Aldose reductase deficiency leads to oxidative stress-induced dopaminergic neuronal loss and autophagic abnormality in an animal model of Parkinson's disease[J]. Neurobiology of Aging, 2017, 50: 119-133.
APA	Yeung，Patrick K.K., Lai，Angela K.W., Son，Hyo Jin., Zhang，Xu., Hwang，Onyou., .. & Chung，Sookja K. (2017). Aldose reductase deficiency leads to oxidative stress-induced dopaminergic neuronal loss and autophagic abnormality in an animal model of Parkinson's disease. Neurobiology of Aging, 50, 119-133.
MLA	Yeung，Patrick K.K.,et al."Aldose reductase deficiency leads to oxidative stress-induced dopaminergic neuronal loss and autophagic abnormality in an animal model of Parkinson's disease". Neurobiology of Aging 50(2017): 119-133.