PI3K is a key molecule in the Nrf2-mediated regulation of antioxidative proteins by hemin in human neuroblastoma cells.
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.
Nakaso
Kazuhiro
K
Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, 36-1, Nishimachi, Yonago 683-8504, Japan. kazuhiro@grape.med.tottori-u.ac.jp
Yano
Hidetaka
H
Fukuhara
Yoko
Y
Takeshima
Takao
T
Wada-Isoe
Kenji
K
Nakashima
Kenji
K
D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D006427:Hemin / Q000502:physiology*; D006801:Humans; D051267:NF-E2-Related Factor 2; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D010544:Peroxidases / Q000378:metabolism*; D054464:Peroxiredoxins; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D013879:Thioredoxins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D015534:Trans-Activators; D013879:Thioredoxins; D006427:Hemin; D010544:Peroxidases; D054464:Peroxiredoxins; D006419:Heme Oxygenase (Decyclizing); D019869:Phosphatidylinositol 3-Kinases