title: Nrf2/ARE Pathway Involved in Oxidative Stress Induced by Paraquat in Human Neural Progenitor Cells.
abstract: Compelling evidences have shown that diverse environmental insults arising during early life can either directly lead to a reduction in the number of dopaminergic neurons or cause an increased susceptibility to neurons degeneration with subsequent environmental insults or with aging alone. Oxidative stress is considered the main effect of neurotoxins exposure. In this study, we investigated the oxidative stress effect of Paraquat (PQ) on immortalized human embryonic neural progenitor cells by treating them with various concentrations of PQ. We show that PQ can decrease the activity of SOD and CAT but increase MDA and LDH level. Furthermore, the activities of Cyc and caspase-9 were found increased significantly at 10 μM of PQ treatment. The cytoplasmic Nrf2 protein expressions were upregulated at 10 μM but fell back at 100 μM. The nuclear Nrf2 protein expressions were upregulated as well as the downstream mRNA expressions of HO-1 and NQO1 in a dose-dependent manner. In addition, the proteins expression of PKC and CKII was also increased significantly even at 1 μM. The results suggested that Nrf2/ARE pathway is involved in mild to moderate PQ-induced oxidative stress which is evident from dampened Nrf2 activity and low expression of antioxidant genes in PQ induced oxidative damage.
authors.affiliation: School of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Dou
authors.affiliation: School of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China.
authors.forename: Mengling
authors.initials: M
authors.lastname: Yan
authors.affiliation: School of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China.
authors.forename: Xinjin
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Lu
authors.affiliation: School of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Zhao
authors.affiliation: School of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Lou
authors.affiliation: School of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Wu
authors.affiliation: School of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Chang
authors.affiliation: School of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000096:biosynthesis / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis / Q000235:genetics; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010269:Paraquat / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D002374:Catalase; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D010269:Paraquat