PI3K is a key molecule in the Nrf2‐mediated regulation of antioxidative proteins by hemin in human neuroblastoma cells

FEBS Letters

Wada-Isoe, Kenji¹  Nakashima, Kenji¹  Fukuhara, Yoko¹  Yano, Hidetaka¹  Takeshima, Takao¹  Nakaso, Kazuhiro¹ 

[1] Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, 36-1, Nishimachi, Yonago 683-8504, Japan

关键词: Phosphatidyl inositol 3-kinase;    NF-E2-related factor 2;    Antioxidant responsive element;    Heme oxygenase-1;    Thioredoxin;    Peroxiredoxin;    PI3K;    phosphatidyl inositol 3-kinase;    Nrf2;    NF-E2-related factor 2;    ARE;    antioxidant responsive element;    HO-1;    heme oxygenase-1;   

DOI  :  10.1016/S0014-5793(03)00517-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Oxidative stress and ferrous metabolism are important in the pathogenesis in Parkinson's disease. In dopaminergic neurons, several stress proteins are upregulated under oxidative stress. To clarify this mechanism, we investigated hemin-related signal transduction and the induction of oxidative stress-related proteins in SH-SY5Y cells. We identified phosphatidylinositol 3-kinase (PI3K) and Nrf2 as important molecules in the induction of heme oxygenase-1, thioredoxin, and peroxiredoxin-I. PI3K-related signal controlled Nrf2 activation, and consequently, PI3K inhibitors blocked the nuclear translocation of Nrf2 and induction of stress proteins. These observations suggest that PI3K and Nrf2 are key molecules in maintaining suitable conditions under oxidative stress and ferrous metabolism.

【 授权许可】

Unknown