A DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine, exacerbates neurotoxicity and upregulates Parkinson's disease-related genes in dopaminergic neurons.

ABSTRACT:

Aims

To investigate effects of DNA methyltransferase (DNMT) inhibitors on dopaminergic neurons and its underlied mechanism.

Methods

The DNMT inhibitor 5-aza-2'-deoxycytidine (5-aza-dC) was tested in cultured dopaminergic cells. Cell viability and apoptosis were assayed with 5-aza-dC alone. Neurotoxicity of 1-methyl-4-phenylpyridinium (MPP(+) ), 6-hydroxydopamine or rotenone was also assayed with 5-aza-dC pretreatment. And mRNA levels of several key PD-related genes were examined by semiquantitative RT-PCR. Furthermore, CpG methylation of α-synuclein promoter was examined by bisulfite sequencing.

Results

5-aza-dC resulted in decreased cell viability and increased apoptosis in dopaminergic neuronal cells. Pretreatment with 5-aza-dC exacerbated neurotoxic damage to dopam

SUBMITTER: Wang Y 

PROVIDER: S-EPMC6493528 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature