科研之友
微信
新浪微博
Facebook
分享链接
摘要
The importance of DNA methylation in neurodegenerative diseases has been increasingly recognized. We explored role of DNA methylation in the pathogenesis of Parkinson's disease in mouse model induced by MPTP. The global DNA methylation levels of substantia nigra region were measured by ELISA Kit. Expression of Dnmt1 and Dnmt3a were measured by Real-time PCR. Genome-wide profile was performed using methylated DNA immunoprecipitation microarray (MeDIP-Chip). Methylation status of differential methylated gene was validated by bisulfate sequencing and expression of differential methylated gene was determined by Real-time PCR. We have demonstrated that global methylation level was significantly decreased while expression levels of Dnmt 1 was significantly increased in substantia nigra region of MPTP-induced mouse model compared to saline controls. Genome-wide DNA methylation analysis detected 48 sites, involving 44 genes, with significantly altered DNA methylation. The abnormal-methylated genes involved in the biological processes concerning signal transduction, molecular transport, transcription modulation, development, cell differentiation, regulation of apoptosis, oxidation reduction and protein catabolism. The methylation levels of promoter region of Uchl1 in substantia nigra region of MPTP-treated mice were significantly higher than that in the saline controls, with significant decreased expression of mRNA and protein. The methylation levels of promoter region of Arih2 in substantia nigra region of MPTP-treated mice were significantly decreased than that in the saline controls, with significant increased expression of mRNA and protein. These results suggested that DNA methylation were altered in substantia nigra region of MPTP-induced PD model. DNA methylation may play important role in the pathogenesis of PD induced by environmental factors such as MPTP.
- 出版日期2015-3
- 单位中南大学
