Akt/Nrf2 Activated Upregulation of Heme Oxygenase-1 Involves in the Role of Rg1 Against Ferrous Iron-Induced Neurotoxicity in SK-N-SH Cells
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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Akt/Nrf2 激活血红素加氧酶 1 的上调参与 Rg1 对抗 SK-N-SH 细胞中二价铁诱导的神经毒性的作用
DOI：
10.1007/s12640-012-9362-3
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发表时间：
2013-07-01
影响因子：
3.7
通讯作者：
Xie, Junxia
中科院分区：
文献类型：
--
作者：
Du, Xixun;Xu, Huamin;Xie, Junxia
铁积累被认为与帕金森病（PD）的发病机制有关。我们前期的研究发现，人参中的主要药理活性成分Rg1通过调节1-甲基-4-苯基-1,2,3,6-四氢吡啶诱导PD小鼠的铁转运蛋白表达，降低黑质铁水平，从而保护多巴胺能神经元。本研究的目的是探讨Rg1对铁诱导的人神经母细胞瘤SK-N-SH细胞神经毒性的细胞保护作用的其他机制。观察到Rg1对100 μ M亚铁诱导的神经毒性细胞活力有显著的拯救作用。Rg1预处理组血红素加氧酶-1 （HO-1）和铜锌超氧化物歧化酶（Cu/Zn SOD）表达上调。Rg1预处理组可诱导HO-1表达上游的Nrf2核易位，激活PI3K/Akt通路。这可以对抗铁诱导的细胞内活性氧的增加和线粒体跨膜电位的降低。这些结果表明，Rg1对铁毒性的神经保护作用可能是通过激活Akt/Nrf2通路，增加Nrf2诱导的HO-1和Cu/Zn SOD的表达而发挥的抗氧化作用。
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 mu M 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.