title: Akt/Nrf2 activated upregulation of heme oxygenase-1 involves in the role of Rg1 against ferrous iron-induced neurotoxicity in SK-N-SH cells.
abstract: Iron accumulation is considered to be involved in the pathogenesis of Parkinson's disease (PD). Our previous studies have observed that Rg1, a major pharmacologically active ingredient from Ginseng, could protect dopaminergic neurons by reducing nigral iron levels through regulating the expression of iron transporters in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mice. The aim of this study is to investigate other mechanism involved in the cytoprotection of Rg1 against iron-induced neurotoxicity in human neuroblastoma SK-N-SH cells. Significant rescue of Rg1 on cell viability against 100 μM ferrous iron-induced neurotoxicity was observed. Upregulation of heme oxygenase-1 (HO-1) and Cu-Zn superoxide dismutase (Cu/Zn SOD) were observed in Rg1 pretreated group. Moreover, Rg1 pretreatment induces Nrf2 nuclear translocation, which is upstream of HO-1 expression, and activated PI3K/Akt pathway was also observed in Rg1 pretreated group. This could antagonize iron-induced increase in intracellular reactive oxygen species and decrease in mitochondrial transmembrane potential. These results suggest that the neuroprotective effects of Rg1 against iron toxicity are attributed to the anti-oxidative properties by activating Akt/Nrf2 pathway and increasing Nrf2-induced expression of HO-1 and Cu/Zn SOD.
authors.affiliation: Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, No. 308 Ningxia Road, Qingdao, 266071, China.
authors.forename: Xixun
authors.initials: X
authors.lastname: Du
authors.forename: Huamin
authors.initials: H
authors.lastname: Xu
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Junxia
authors.initials: J
authors.lastname: Xie
mesh_terms: D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D005296:Ferrous Compounds / Q000037:antagonists & inhibitors* / Q000633:toxicity; D036145:Ginsenosides / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D005296:Ferrous Compounds; D036145:Ginsenosides; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; C020748:ferrous sulfate; D007501:Iron; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt