DNA demethylation upregulated Nrf2 expression in Alzheimer's disease cellular model

Frontiers in Aging Neuroscience

Gang eYu¹  Beibei eChen¹  Yushuang eDeng¹  Huimin eCao¹  Xi eLu¹  Li eWang²  Xiuming eGuo³  Peng eZheng³  Yi eHe³  Yuping eZhang³  Yubin eDing⁵  Yu eLi⁶ 

[1] Chongqing Key Laborotary of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China.;Department of Bio-therapy and Hemato-oncology, Chongqing Cancer Institute;Department of Neurology, The First Affiliated Hospital of Chongqing Medical University;Department of Pathology, Chongqing Medical University;Department of Reproductive Biology, Chongqing Medical University, Chongqing, 400016, People’s Republic of China.;Institute of Neuroscience, Chongqing Medical University;

关键词: Oxidative Stress;    Alzheimer's disease;    Nrf2;    DNA demethylation;    NQO1;    Cellular model;   

DOI  :  10.3389/fnagi.2015.00244

来源: DOAJ

【 摘 要 】

Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important transcription factor in the defense against oxidative stress. Cumulative evidence has shown that oxidative stress plays a key role in the pathogenesis of Alzheimer's disease (AD). Previous animal and clinical studies had observed decreased expression of Nrf2 in AD. However, the underlying regulation mechanisms of Nrf2 in AD remain unclear. Here, we used the DNA methyltransferases (Dnmts) inhibitor 5-aza-2′-deoxycytidine (5-Aza) to test whether Nrf2 expression was regulated by methylation in N2a cells characterizing by expressing human Swedish mutant amyloid precursor protein (N2a/APPswe). We found 5-Aza treatment increased Nrf2 at both mRNA and protein levels via down-regulating the expression of Dnmts and DNA demethylation. In addition, 5-Aza mediated upregulation of Nrf2 expression was concomitant with increased nuclear translocation of Nrf2 and higher expression of Nrf2 downstream target gene NAD(P)H:quinone oxidoreductas (NQO1). Our study showed that DNA demethylation promoted the Nrf2 cell signaling pathway, which may enhance the antioxidant system against AD development.

【 授权许可】

Unknown