Parkinson's disease related gene PINK1 but not DJ-1 was down-regulated in neurotoxicity of 6-hydroxydopamine and 1-methyl-4-phenylpyridinium

doi:10.3969/j.issn.1006-7795.2015.05.015

Journal of Capital Medical University ›› 2015, Vol. 36 ›› Issue (5): 740-746.doi: 10.3969/j.issn.1006-7795.2015.05.015

Previous Articles Next Articles

Parkinson's disease related gene PINK1 but not DJ-1 was down-regulated in neurotoxicity of 6-hydroxydopamine and 1-methyl-4-phenylpyridinium

Yang Jian^1,2, Wang Yong^2,3, Wang Xuan^2,3, Yang Zhaofei^1,2, Gong Xiaoli^2,3, Wang Xiaomin^1,2

1. Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China;
2. Beijing Institute for Brain Disorders, Beijing 100069, China;
3. Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Department of Physiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China

Received:2015-09-14 Online:2015-10-21 Published:2015-10-20
Contact: 王晓民 E-mail:xmwang@ccmu.edu.cn
Supported by:
This study was supported by Major State Basic Research Development Program of the China (973 Program) (2011CB504100), Natural Science Foundation of Beijing (7082008), Project of Construction of Innovative Teams and Teacher Career Development for Universities and Colleges under Beijing Municipal Education Commission (IDHT20140514).

Abstract

Abstract: Objective To explore the transcriptional levels and molecular mechanism of key Parkinson's disease (PD)-related genes DJ-1 and PINK1 in neurotoxicity. Methods MN9D cells were used as dopaminergic neurons and treated with neurotoxins 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP⁺). Lethal doses 50 (LD 50) was determined by cell counting with Typan Blue staining. Transcriptional levels of DJ-1, PINK1 and demethylation enzyme TET1 were detected by semi-quantitative RT-PCR. Expressional levels of demethylation enzyme TET1 were detected by immune-cytofluorescent staining. Results LD50 at 10 μmol/L of 6-OHDA and 100 μmol/L of MPP⁺ were used to treat MN9D cells. In neurotoxicity of 6-OHDA and MPP⁺, transcriptional levels of PINK1 were significantly down-regulated, but no change in DJ-1 transcriptional levels was found. In addition, transcriptional and expressional levels of TET1 were down-regulated in neurotoxicity of 6-OHDA and MPP⁺. Conclusion These data suggest that down-regulated TET1 might contribute to the down-regulation of PINK1 in neurotoxicity of PD.

Key words: Parkinson's disease, neurotoxicity, PINK1, DJ-1, Ten-eleven translocation 1

CLC Number:

Yang Jian, Wang Yong, Wang Xuan, Yang Zhaofei, Gong Xiaoli, Wang Xiaomin. Parkinson's disease related gene PINK1 but not DJ-1 was down-regulated in neurotoxicity of 6-hydroxydopamine and 1-methyl-4-phenylpyridinium[J]. Journal of Capital Medical University, 2015, 36(5): 740-746.

0
/ / Recommend

Add to citation manager EndNote|Reference Manager|ProCite|BibTeX|RefWorks

URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2015.05.015

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2015/V36/I5/740

References

[1] Ali S F, Binienda Z K, Imam S Z. Molecular aspects of dopaminergic neurodegeneration: gene-environment interaction in parkin dysfunction[J]. Int J Environ Res Public Health, 2011, 8(12):4702-4713.
[2] Hauser D N, Hastings T G. Mitochondrial dysfunction and oxidative stress in Parkinson's disease and monogenic parkinsonism[J]. Neurobiol Dis, 2013, 51:35-42.
[3] Yu W, Sun Y, Guo S, et al. The PINK1/Parkin pathway regulates mitochondrial dynamics and function in mammalian hippocampal and dopaminergic neurons[J]. Hum Mol Genet, 2011, 20(16):3227-3240.
[4] Giaime E, Yamaguchi H, Gautier C A, et al. Loss of DJ-1 does not affect mitochondrial respiration but increases ROS production and mitochondrial permeability transition pore opening[J]. PLoS One, 2012, 7(7):e40501.
[5] Huidobro C, Fernandez A F, Fraga M F, et al. Aging epigenetics: causes and consequences[J]. Mol Aspects Med, 2013, 34(4):765-781.
[6] Kaas G A, Zhong C, Eason D E, et al. TET1 controls CNS 5-methylcytosine hydroxylation, active DNA demethylation, gene transcription, and memory formation[J]. Neuron, 2013, 79(6):1086-1093.
[7] Rudenko A, Dawlaty M M, Seo J, et al. Tet1 is critical for neuronal activity-regulated gene expression and memory extinction[J]. Neuron, 2013, 79(6):1109-1122.
[8] Zhang H, Zhang X, Clark E, et al. TET1 is a DNA-binding protein that modulates DNA methylation and gene transcription via hydroxylation of 5-methylcytosine[J]. Cell Res, 2010, 20 (12): 1390-1393.
[9] Dias V, Junn E, Mouradian M M. The role of oxidative stress in Parkinson's disease[J]. J Parkinsons Dis, 2013, 3(4):461-491.
[10] Bove J, Prou D, Perier C, et al. Toxin-induced models of Parkinson's disease[J]. NeuroRx, 2005, 2(3):484-494.
[11] Lancu R, Mohapel P, Brundin P, et al. Behavioral characterization of a unilateral 6-OHDA-lesion model of Parkinson's disease in mice[J]. Behav Brain Res, 2005, 162(1):1-10.
[12] Yuan H, Sarre S, Ebinger G, et al. Histological, behavioural and neurochemical evaluation of medial forebrain bundle and striatal 6-OHDA lesions as rat models of Parkinson's disease[J]. J Neurosci Methods, 2005, 144(1):35-45.
[13] Luo D, Zhang Q, Wang H, et al. Fucoidan protects against dopaminergic neuron death in vivo and in vitro[J]. Eur J Pharmacol, 2009, 617(1-3):33-40.
[14] Jackson-Lewis V, Przedborski S. Protocol for the MPTP mouse model of Parkinson's disease[J]. Nat Protoc, 2007, 2(1):141-151.
[15] Grunblatt E, Mandel S, Jacob-Hirsch J, et al. Gene expression profiling of parkinsonian substantia nigra pars compacta; alterations in ubiquitin-proteasome, heat shock protein, iron and oxidative stress regulated proteins, cell adhesion/cellular matrix and vesicle trafficking genes[J]. J Neural Transm, 2004, 111(12):1543-1573.
[16] Bandopadhyay R, Kingsbury A E, Cookson M R, et al. The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson's disease[J]. Brain, 2004, 127 (Pt2):420-430.
[17] Gandhi S, Muqit M M, Stanyer L, et al. PINK1 protein in normal human brain and Parkinson's disease[J]. Brain, 2006, 129 (Pt7):1720-1731.
[18] Villeneuve L M, Purnell P R, Boska M D, et al. Early expression of parkinson,s disease-related mitochondrial abnormalities in PINK1 knockout rats[J]. Mol Neurobiol, 2014 Nov 25.[EPub ahead of Print]
[19] Tahiliani M, Koh K P, Shen Y, et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1[J]. Science, 2009, 324(5929): 930-935.
[20] Ito S, D,Alessio A C, Taranova O V, et al. Role of Tet proteins in 5 mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification[J]. Nature, 2010, 466( 7310):1129- 1133.
[21] Chouliaras L, Mastroeni D, Delvaux E, et al. Consistent decrease in global DNA methylation and hydroxymethylation in the hippocampus of Alzheimer's disease patients[J]. Neurobiol Aging, 2013, 34(9): 2091-2099.

Parkinson's disease related gene PINK1 but not DJ-1 was down-regulated in neurotoxicity of 6-hydroxydopamine and 1-methyl-4-phenylpyridinium

PDF

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 3

Recommended Articles

Metrics

Comments

[1]	Zhang Zhili, Chen Binggang, Jiang Taiyi, Qiao Luxin, Wu Hao, Chen Dexi, Zhang Yulin. Neurotoxicity of HIV-1 envelope protein gp120 V3 loop [J]. Journal of Capital Medical University, 2014, 35(1): 87-91.
[2]	Zhang Jie;Li Jie;Wu Ping. Role of Oxidative Stress in Manganese-induced Neurotoxicity [J]. Journal of Capital Medical University, 2008, 29(5): 664-667.
[3]	Chen Li;Wu Ping;Zhang Jie;Li Jie;Xuan Dengfeng;Chu Jinhua;Zhao Feng;Li Guojun. Neural Toxicity Induced by Divalent and Tetravalent Forms of Manganese and its Protection by Selenium [J]. Journal of Capital Medical University, 2005, 26(6): 652-654.