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

被引:292
作者
Nakaso, K [1 ]
Yano, H [1 ]
Fukuhara, Y [1 ]
Takeshima, T [1 ]
Wada-Isoe, K [1 ]
Nakashima, K [1 ]
机构
[1] Tottori Univ, Fac Med, Inst Neurol Sci, Dept Neurol, Yonago, Tottori 6838504, Japan
关键词
phosphatidyl inositol 3-kinase; NF-E2-related factor 2; antioxidant responsive element; heme oxygenase-1; thioredoxin; peroxiredoxin;
D O I
10.1016/S0014-5793(03)00517-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
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. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.
引用
收藏
页码:181 / 184
页数:4
相关论文
共 33 条
[1]
Thioredoxin suppresses 1-methyl-4-phenylpyridinium-induced neurotoxicity in rat PC12 cells [J].
Bai, J ;
Nakamura, H ;
Hattori, I ;
Tanito, M ;
Yodoi, J .
NEUROSCIENCE LETTERS, 2002, 321 (1-2) :81-84
[2]
Oxidatively modified proteins in aging and disease [J].
Beal, MF .
FREE RADICAL BIOLOGY AND MEDICINE, 2002, 32 (09) :797-803
[3]
Transcription-dependent and -independent control of neuronal survival by the PI3K-Akt signaling pathway [J].
Brunet, A ;
Datta, SR ;
Greenberg, ME .
CURRENT OPINION IN NEUROBIOLOGY, 2001, 11 (03) :297-305
[4]
The phosphoinositide 3-kinase pathway [J].
Cantley, LC .
SCIENCE, 2002, 296 (5573) :1655-1657
[5]
CHAE HZ, 1994, J BIOL CHEM, V269, P27670
[6]
CONNOR JR, 1995, J NEUROCHEM, V65, P717
[7]
Thioredoxin, a singlet oxygen quencher and hydroxyl radical scavenger: Redox independent functions [J].
Das, KC ;
Das, CK .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 277 (02) :443-447
[8]
Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants [J].
Dinkova-Kostova, AT ;
Holtzclaw, WD ;
Cole, RN ;
Itoh, K ;
Wakabayashi, N ;
Katoh, Y ;
Yamamoto, M ;
Talalay, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (18) :11908-11913
[9]
Activation of the mouse heme oxygenase-1 gene by 15-deoxy-Δ12,14-prostaglandin J2 is mediated by the stress response elements and transcription factor Nrf2 [J].
Gong, PF ;
Stewart, D ;
Hu, B ;
Ning, L ;
Cook, J ;
Nel, A ;
Alam, J .
ANTIOXIDANTS & REDOX SIGNALING, 2002, 4 (02) :249-257
[10]
Cobalt induces heme oxygenase-1 expression by a hypoxia-inducible factor-independent mechanism in Chinese hamster ovary cells - Regulation by Nrf2 and MafG transcription factors [J].
Gong, PF ;
Hu, B ;
Stewart, D ;
Ellerbe, M ;
Figueroa, YG ;
Blank, V ;
Beckman, BS ;
Alam, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (29) :27018-27025