The role of Nrf2 in protection against Pb-induced oxidative stress and apoptosis in SH-SY5Y cells.
Lead exerts severe adverse effects on the nervous system in which oxidative stress might mediate impairments. In this study, we focused on Nrf2, which has been identified to significantly influence the protection of a cellular system against many xenobiotic compounds. We found that PbAc exhibited neurotoxicity mainly through oxidant-based processes and could be inhibited by NAC and DPI in SH-SY5Y cells. As a defense response, Nrf2 was activated when exposed to PbAc, thereby inducing a rapid increase in Nrf2 nuclear accumulation, as well as Nrf2-ARE binding activities in a ROS-dependent manner. Analysis of Nrf2-regulated gene expression and protein showed that PbAc could induce the mRNA transcription of HO-1, GSTα1, GCLM, GCLC, and NQO1, as well as the protein expression of HO-1 and γ-GCS. The responses of these genes to PbAc were regulated by Nrf2. Silencing Nrf2 expression in SH-SY5Y cells inhibited PbAc-induced gene transcription and protein expression. Overexpression of Nrf2 led to decreased ROS production and cell apoptosis, as well as increased cell viability under PbAc exposure. These results indicated that the Nrf2-ARE system exhibited a protective role in Pb-induced neurotoxicity, providing potential therapeutic strategies for the prevention and treatment of Pb-related diseases.
Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China; Ministry of Education, Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
Fang
F
Ye
Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China; Ministry of Education, Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
Xiaoyi
X
Li
Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China; Ministry of Education, Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
Lili
L
Li
Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China; Ministry of Education, Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
Ling
L
Lyu
Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China; Ministry of Education, Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China. Electronic address: jyuan@tjh.tjmu.edu.cn.
Jing
J
Yuan
Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China; Ministry of Education, Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China. Electronic address: chen-jun@hust.edu.cn.
Jun
J
Chen
D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation / Q000502:physiology*; D020868:Gene Silencing; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D009942:Organometallic Compounds / Q000633:toxicity*; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species
D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D009942:Organometallic Compounds; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C008261:lead acetate
Antioxidant gene; Lead; Neurotoxicity; Nrf2; Oxidative stress