AP endonuclease 1 (Apex1) influences brain development linking oxidative stress and DNA repair
文献类型:期刊论文
作者 | Pei, De-Sheng1,2![]() |
刊名 | CELL DEATH & DISEASE
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出版日期 | 2019-04-25 |
卷号 | 10页码:14 |
ISSN号 | 2041-4889 |
DOI | 10.1038/s41419-019-1578-1 |
通讯作者 | Pei, De-Sheng(deshengpei@gmail.comM) ; Strauss, Phyllis R.(p.strauss@northeastern.edu) |
英文摘要 | Brain and neurons are particularly sensitive to reactive oxygen species (ROS). Oxidative damage from ROS results in increased 8-oxoguanine in DNA followed by repair through the base excision repair (BER) pathway. We reported earlier that AP endonuclease 1 (Apex1) not only participates directly in BER but also regulates transcription factor Creb1. Here, we investigated how Apex1 affects brain to respond effectively to oxidative damage during zebrafish development. Loss of Apex1 resulted in increased ROS, 8-oxoguanine, and abasic sites as well as loss of Ogg1, which recognizes 8-oxoguanine and is required for its repair. Moreover, knock-down of Apex1 not only resulted in reduction of expression of several major proteins in the BER pathway (Polb and Ogg1), and it also resulted in maldistribution and loss of four key brain transcription factors (fezf2, otx2, egr2a, and pax2a), leading to abnormal brain development. These results were independent of p53 protein level. In contrast, exposure to exogenous H2O2 resulted in increased transcription and protein of Apex1 along with other BER components, as well as Creb1. Taken together, these results indicate that oxidative stress increased when the level of Apex1 was reduced, revealing a novel pathway of how Apex1 manages oxidative stress in developing brain. |
资助项目 | CAS Team Project of the Belt and Road ; G. Harold and Leila Y. Mathers Charitable Foundation ; Northeastern University ; Three Hundred Leading Talents in Scientific and Technological Innovation Program of Chongqing[CSTCCXLJRC201714] ; Program of China-Sri Lanka Joint Research and Demonstration Center for Water Technology ; China-Sri Lanka Joint Center for Education and Research by Chinese Academy of Sciences, China |
WOS研究方向 | Cell Biology |
语种 | 英语 |
WOS记录号 | WOS:000468665400004 |
出版者 | NATURE PUBLISHING GROUP |
源URL | [http://119.78.100.138/handle/2HOD01W0/7886] ![]() |
专题 | 环境与健康研究中心 |
通讯作者 | Pei, De-Sheng; Strauss, Phyllis R. |
作者单位 | 1.Henan Normal Univ, Coll Life Sci, Xinxiang 453007, Peoples R China 2.Chinese Acad Sci, Chongqing Inst Green & Intelligent Technol, Key Lab Reservoir Aquat Environm, Chongqing 400714, Peoples R China 3.Northeastern Univ, Coll Sci, Dept Biol, Boston, MA 02115 USA |
推荐引用方式 GB/T 7714 | Pei, De-Sheng,Jia, Pan-Pan,Luo, Juan-Juan,et al. AP endonuclease 1 (Apex1) influences brain development linking oxidative stress and DNA repair[J]. CELL DEATH & DISEASE,2019,10:14. |
APA | Pei, De-Sheng,Jia, Pan-Pan,Luo, Juan-Juan,Liu, Wei,&Strauss, Phyllis R..(2019).AP endonuclease 1 (Apex1) influences brain development linking oxidative stress and DNA repair.CELL DEATH & DISEASE,10,14. |
MLA | Pei, De-Sheng,et al."AP endonuclease 1 (Apex1) influences brain development linking oxidative stress and DNA repair".CELL DEATH & DISEASE 10(2019):14. |
入库方式: OAI收割
来源:重庆绿色智能技术研究院
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