L-DOPA regulates MAO-B transcription through DNA methylation in SH-SY5Y cells

doi:10.3969/j.issn.1006-7795.2015.05.014

Journal of Capital Medical University ›› 2015, Vol. 36 ›› Issue (5): 734-739.doi: 10.3969/j.issn.1006-7795.2015.05.014

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L-DOPA regulates MAO-B transcription through DNA methylation in SH-SY5Y cells

Yang Zhaofei^1,2, Wang Yong^2,3, Yang Jian^1,2, Wang Xuan^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:2015-08-03 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 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 Municipality (IDHT20140514).

Abstract

Abstract: Objective To explore the effect and molecular mechanism of L-3,4-dihydroxyphenylalanine (L-DOPA) on transcription of monoamine oxidase B (MAO-B), which was a key gene in dopamine metabolisms. Methods SH-SY5Y cells were used as the object to mimic dopaminergic neurons in Parkinson's disease. Methylated DNA quantitation kit was used to analyze genomic 5-mC content. The gene transcriptional levels were measured by semi-quantitative RT-PCR. Methylation specific PCR (MSP) was applied to detect the promotor CpG methylation status of MAO-B. Results 1 Genomic 5-mC content was decreased in SH-SY5Y cells treated with L-DOPA (2 μmol/L and 20 μmol/L) for 24 h. 2 Monoamine oxidase B (MAO-B) mRNA level was significantly down-regulation in L-dopa administration, but neither DOPA-decarboxylase (DDC) nor catechol-O-methyltransferase (COMT). 3 A DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (5-aza-dC), induced MAO-B mRNA level up-regulation, but COMT and DDC mRNA levels did not affected. 4 CpG hyper-methylation of MAO-B was induced by L-DOPA (2 μmol/L and 20 μmol/L) for 24 h. And CpG hypo-methylation was induced by 5-aza-dC. Conclusion Transcription of MAO-B was down-regulated by L-DOPA and might be mediated by L-DOPA induced promoter CpG hyper-methylation. This study might provide a new evidence in the view of epigenetics, especially DNA methylation, on dopamine dysregulation and L-DOPA induced side effects in clinic.

Key words: L-3,4-dihydroxyphenylalanine, monoamine oxidase B, DNA methylation, gene transcription

CLC Number:

Yang Zhaofei, Wang Yong, Yang Jian, Wang Xuan, Wang Xiaomin. L-DOPA regulates MAO-B transcription through DNA methylation in SH-SY5Y cells[J]. Journal of Capital Medical University, 2015, 36(5): 734-739.

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L-DOPA regulates MAO-B transcription through DNA methylation in SH-SY5Y cells

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