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01-05-2012

Upregulation of Heme Oxygenase-1 by Acteoside Through ERK and PI3 K/Akt Pathway Confer Neuroprotection Against Beta-Amyloid-Induced Neurotoxicity

Authors: Hong-Quan Wang, Yu-Xia Xu, Cui-Qing Zhu

Published in: Neurotoxicity Research | Issue 4/2012

Abstract

Our previous study has shown that acteoside, an antioxidative phenylethanoid glycoside, protect against beta-amyloid (Aβ)-induced cytotoxicity in vitro. However, the precise protective mechanisms remains unclear. Heme oxygenase-1 (HO-1) is a crucial factor in the response to oxidative injury, protecting neurons against Aβ-induced injury. In the present study we examined to determine whether acteoside upregulates HO-1 expression, and thereby protects PC12 cells against Aβ-induced cell death. It was revealed that acteoside is an activator of Nrf2 and inducer of HO-1 expression. We showed that acteoside increased HO-1 expression in vitro and in vivo. Acteoside treatment resulted in nuclear translocation of the transcription factor NF-E2-related factor 2 (Nrf2). Acteoside activated both ERK and PI3 K/Akt, and treatments with the specific ERK inhibitor PD98059, the PI3 K inhibitor LY294002, and the specific Nrf2 siRNA suppressed the acteoside-induced HO-1 expression. The HO-1 inhibitor ZnPP, PD98059, and LY294002 markedly abolished the neuroprotective effect of acteoside against Aβ-induced neurotoxicity. Taken together, these results demonstrate that acteoside is an activator of Nrf2 and inducer of HO-1 expression. We also showed that acteoside increased HO-1 expression through activation of ERK and PI3 K/Akt signal pathways in vitro. Upregulation of HO-1 by acteoside may involve in the neuroprotection against Aβ-induced neurotoxicity.

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Title: Upregulation of Heme Oxygenase-1 by Acteoside Through ERK and PI3 K/Akt Pathway Confer Neuroprotection Against Beta-Amyloid-Induced Neurotoxicity
Authors: Hong-Quan Wang
Yu-Xia Xu
Cui-Qing Zhu
Publication date: 01-05-2012
Publisher: Springer-Verlag
Published in: Neurotoxicity Research / Issue 4/2012
Print ISSN: 1029-8428
Electronic ISSN: 1476-3524
DOI: https://doi.org/10.1007/s12640-011-9292-5

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Upregulation of Heme Oxygenase-1 by Acteoside Through ERK and PI3 K/Akt Pathway Confer Neuroprotection Against Beta-Amyloid-Induced Neurotoxicity

Abstract

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Abstract

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