5'-Aza-dC sensitizes paraquat toxic effects on PC12 cell.
Parkinson's disease (PD) is one of the common neurodegenerative diseases that result in the progressive damage of dopaminergic neurons. Environmental exposure, including paraquat, is considered risky for PD. Epigenetics refer to the study of heritable changes in gene expression that occur without a change in DNA sequence. Epigenetic abnormalities (e.g. DNA methylation) have also been found to be causative factors in aging disease, such as PD. How these risk factors cooperate to induce progressive neurodegeneration in PD remains largely unknown. In this study, the PC12 cells was pretreated with methyltransferase inhibitor 5'-aza-2-deoxycytidi(5'-aza-dC) for 24 h, then exposed to paraquat for 12h. The biochemical mechanisms were investigated. The results showed that cell activity remarkably decreased and apoptotic cells increased after paraquat plus 5'-aza-dC treatment. Moreover, compared with paraquat treatment alone, after being exposed to paraquat plus 5'-aza-dC, the level of reactive oxygen species (ROS) increased significantly. The expression of bcl-2 decreased, expressions of bax increased, the rate of bcl-2/bax decreased, and thus expressions of cytochrome C increased. Our findings suggest that 5'-aza-dC modulating DNA methylation could sensitize paraquat toxic effects on PC12 cell by oxidative stress increment and mitochondrial deficit. Demonstration of the interaction of DNA methylation and paraquat provides additional new insights into the pathogenic mechanisms of PD.
Department of Neurology, Yantaishan Hospital, Yantai City, Shandong 264000, PR China.
Min
M
Kong
Maowen
M
Ba
Hui
H
Liang
Lili
L
Ma
Quntao
Q
Yu
Tianxia
T
Yu
Ying
Y
Wang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors*; D000077209:Decitabine; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism; D006540:Herbicides / Q000633:toxicity*; D024101:Mitochondrial Proteins / Q000378:metabolism; D016716:PC12 Cells; D010269:Paraquat / Q000633:toxicity*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D006540:Herbicides; D024101:Mitochondrial Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D000077209:Decitabine; D045304:Cytochromes c; D015254:DNA Modification Methylases; D001374:Azacitidine; D010269:Paraquat