title: Ferulic Acid Protects Against Lead Acetate-Induced Inhibition of Neurite Outgrowth by Upregulating HO-1 in PC12 Cells: Involvement of ERK1/2-Nrf2 Pathway.
abstract: Prenatal lead exposure is associated with poor intellectual development in children. However, there are few breakthroughs in therapeutic intervention of developmental lead neurotoxicity. The aim of this study is to evaluate the hypothesis that ferulic acid-mediated promotion of neurite outgrowth following lead exposure might mainly result from its antioxidant capability by extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation of nuclear factor erythroid 2-related factor 2 (Nrf2). Exposure of PC12 cells to lead acetate inhibits neurite outgrowth and causes oxidative stress as measured by ROS, LPO, GSH/GSSG, and NAD+/NADH. FA treatment significantly, although not completely, protected the cells against lead acetate-induced neurite outgrowth inhibition. The effects of FA could be blocked by PD98059, zinc protoporphyrin (Zn-PP), and Nrf2 shRNA. In addition, FA induced heme oxygenase 1 (HO-1) gene expression, enhanced antioxidant response element (ARE) promoter activity, promoted ERK1/2 phosphorylation, and Nrf2 translocation in PC12 cells exposed to lead acetate. ERK1/2 locate upstream of Nrf2 and regulate Nrf2-dependent HO-1 expression in antioxidative effects of FA. Our results suggest that FA is a promising candidate for treatment of developmental lead neurotoxicity. These promising findings warrant future investigation evaluating the FA-mediated potentiation of neurite outgrowth following lead exposure in vivo.
authors.affiliation: The Institute of Medicine, Qiqihar Medical University, 333 BuKui Street, JianHua District, Qiqihar, 161006, China.
authors.forename: Chun-Lei
authors.initials: CL
authors.lastname: Yu
authors.affiliation: The Institute of Medicine, Qiqihar Medical University, 333 BuKui Street, JianHua District, Qiqihar, 161006, China.
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Zhao
authors.affiliation: The Institute of Medicine, Qiqihar Medical University, 333 BuKui Street, JianHua District, Qiqihar, 161006, China. nyc1968@126.com.
authors.forename: Ying-Cai
authors.initials: YC
authors.lastname: Niu
mesh_terms: D000818:Animals; D061745:Antioxidant Response Elements; D003373:Coumaric Acids / Q000737:chemistry / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D008954:Models, Biological; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D000071446:Neuronal Outgrowth / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology; D009942:Organometallic Compounds; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D003373:Coumaric Acids; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; D009942:Organometallic Compounds; C004999:ferulic acid; D051547:Heme Oxygenase-1; D048052:Mitogen-Activated Protein Kinase 3; C008261:lead acetate
keywords: ERK1/2; Ferulic acid; Lead neurotoxicity; Neurite outgrowth; Oxidative stress