Strong evidence indicates oxidative stress in the pathogenesis of Alzheimer's disease (AD). Amyloid beta (A beta) has been implicated in both oxidative stress mechanisms and in neuronal apoptosis. Glutaredoxin-1 (GRX1) and thioredoxin-1 (TRX1) are antioxidants that can inhibit apoptosis signal-regulating kinase (ASK1). We examined levels of GRX1 and TRX1 in AD brain as well as their effects on Ab neurotoxicity. We show an increase in GRX1 and a decrease in neuronal TRX1 in AD brains. Using SH-SY5Y cells, we demonstrate that A beta causes an oxidation of both GRX1 and TRX1, and nuclear export of Daxx, a protein downstream of ASK1. Ab toxicity was inhibited by insulin-like growth factor-I (IGF-I) and by overexpressing GRX1 or TRX1. Thus, A beta neurotoxicity might be mediated by oxidation of GRX1 or TRX1 and subsequent activation of the ASK1 cascade. Deregulation of GRX1 and TRX1 antioxidant systems could be important events in AD pathogenesis.
机构:
Karolinska Univ Hosp Huddinge, Karolinska Inst, Dept Lab Med, Div Pathol, SE-14186 Stockholm, SwedenKarolinska Univ Hosp Huddinge, Karolinska Inst, Dept Lab Med, Div Pathol, SE-14186 Stockholm, Sweden
Arodin, Lisa
Lamparter, Heidrun
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Heidelberg Univ, Sect Geriatr Psychiat, Heidelberg, GermanyKarolinska Univ Hosp Huddinge, Karolinska Inst, Dept Lab Med, Div Pathol, SE-14186 Stockholm, Sweden
Lamparter, Heidrun
Karlsson, Hakan
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Karolinska Inst, Dept Neurosci, Stockholm, SwedenKarolinska Univ Hosp Huddinge, Karolinska Inst, Dept Lab Med, Div Pathol, SE-14186 Stockholm, Sweden
Karlsson, Hakan
Nennesmo, Inger
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Karolinska Univ Hosp Huddinge, Karolinska Inst, Dept Lab Med, Div Pathol, SE-14186 Stockholm, SwedenKarolinska Univ Hosp Huddinge, Karolinska Inst, Dept Lab Med, Div Pathol, SE-14186 Stockholm, Sweden
Nennesmo, Inger
Bjoernstedt, Mikael
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Karolinska Univ Hosp Huddinge, Karolinska Inst, Dept Lab Med, Div Pathol, SE-14186 Stockholm, SwedenKarolinska Univ Hosp Huddinge, Karolinska Inst, Dept Lab Med, Div Pathol, SE-14186 Stockholm, Sweden
Bjoernstedt, Mikael
Schroder, Johannes
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Heidelberg Univ, Sect Geriatr Psychiat, Heidelberg, GermanyKarolinska Univ Hosp Huddinge, Karolinska Inst, Dept Lab Med, Div Pathol, SE-14186 Stockholm, Sweden
Schroder, Johannes
Fernandes, Aristi P.
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Karolinska Univ Hosp Huddinge, Karolinska Inst, Dept Lab Med, Div Pathol, SE-14186 Stockholm, SwedenKarolinska Univ Hosp Huddinge, Karolinska Inst, Dept Lab Med, Div Pathol, SE-14186 Stockholm, Sweden
机构:
Faculty of Environmental Science and Engineering,Kunming University of Science and Technology
Medical School,Kunming University of Science and TechnologyFaculty of Environmental Science and Engineering,Kunming University of Science and Technology
BAI Li-ping
LI Ye
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Medical School,Kunming University of Science and TechnologyFaculty of Environmental Science and Engineering,Kunming University of Science and Technology
LI Ye
ZHOU Xiao-shuang
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Medical School,Kunming University of Science and TechnologyFaculty of Environmental Science and Engineering,Kunming University of Science and Technology
ZHOU Xiao-shuang
ZHANG Xian-wen
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Medical School,Kunming University of Science and TechnologyFaculty of Environmental Science and Engineering,Kunming University of Science and Technology
ZHANG Xian-wen
SUN Bo
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Medical School,Kunming University of Science and TechnologyFaculty of Environmental Science and Engineering,Kunming University of Science and Technology
SUN Bo
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YAN Chen
DENG Ru-hua
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Medical School,Kunming University of Science and TechnologyFaculty of Environmental Science and Engineering,Kunming University of Science and Technology
DENG Ru-hua
BAI Jie
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Medical School,Kunming University of Science and TechnologyFaculty of Environmental Science and Engineering,Kunming University of Science and Technology
机构:
Case Western Reserve Univ, Sch Med, Dept Pharmacol, WRT 300,2109 Adelbert Rd, Cleveland, OH 44106 USACase Western Reserve Univ, Sch Med, Dept Pharmacol, WRT 300,2109 Adelbert Rd, Cleveland, OH 44106 USA
Miller, Olga Gorelenkova
Behring, Jessica Belle
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机构:
Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Vasc Biol Sect, Boston, MA 02118 USACase Western Reserve Univ, Sch Med, Dept Pharmacol, WRT 300,2109 Adelbert Rd, Cleveland, OH 44106 USA
Behring, Jessica Belle
Siedlak, Sandra L.
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Case Western Reserve Univ, Sch Med, Dept Pathol, Cleveland, OH 44106 USACase Western Reserve Univ, Sch Med, Dept Pharmacol, WRT 300,2109 Adelbert Rd, Cleveland, OH 44106 USA
Siedlak, Sandra L.
Jiang, Sirui
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Case Western Reserve Univ, Sch Med, Dept Pathol, Cleveland, OH 44106 USACase Western Reserve Univ, Sch Med, Dept Pharmacol, WRT 300,2109 Adelbert Rd, Cleveland, OH 44106 USA
Jiang, Sirui
Matsui, Reiko
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Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Vasc Biol Sect, Boston, MA 02118 USACase Western Reserve Univ, Sch Med, Dept Pharmacol, WRT 300,2109 Adelbert Rd, Cleveland, OH 44106 USA
Matsui, Reiko
Bachschmid, Markus M.
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Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Vasc Biol Sect, Boston, MA 02118 USACase Western Reserve Univ, Sch Med, Dept Pharmacol, WRT 300,2109 Adelbert Rd, Cleveland, OH 44106 USA
Bachschmid, Markus M.
Zhu, Xiongwei
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机构:
Case Western Reserve Univ, Sch Med, Dept Pathol, Cleveland, OH 44106 USACase Western Reserve Univ, Sch Med, Dept Pharmacol, WRT 300,2109 Adelbert Rd, Cleveland, OH 44106 USA
Zhu, Xiongwei
Mieyal, John J.
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机构:
Case Western Reserve Univ, Sch Med, Dept Pharmacol, WRT 300,2109 Adelbert Rd, Cleveland, OH 44106 USA
Louis Stokes Cleveland Vet Adm Med Res Ctr, Cleveland, OH USACase Western Reserve Univ, Sch Med, Dept Pharmacol, WRT 300,2109 Adelbert Rd, Cleveland, OH 44106 USA