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Akt/Nrf2 Activated Upregulation of Heme Oxygenase-1 Involves in the Role of Rg1 Against Ferrous Iron-Induced Neurotoxicity in SK-N-SH Cells

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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.

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Acknowledgments

This work was supported by Grants from the National Program of Basic Research sponsored by the Ministry of Science and Technology of China (2011CB504102), the National Foundation of Natural Science of China (30930036, 81100955), and Qingdao Municipal Science and Technology Commission (10-3-3-1-3-nsh).

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Authors and Affiliations

  1. 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

    Xixun Du, Huamin Xu, Hong Jiang & Junxia Xie

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  1. Xixun Du
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  2. Huamin Xu
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  3. Hong Jiang
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  4. Junxia Xie
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Correspondence to Junxia Xie.

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Du, X., Xu, H., Jiang, H. et al. Akt/Nrf2 Activated Upregulation of Heme Oxygenase-1 Involves in the Role of Rg1 Against Ferrous Iron-Induced Neurotoxicity in SK-N-SH Cells. Neurotox Res 24, 71–79 (2013). https://doi.org/10.1007/s12640-012-9362-3

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