title: Upregulation of heme oxygenase-1 by acteoside through ERK and PI3 K/Akt pathway confer neuroprotection against beta-amyloid-induced neurotoxicity.
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.
authors.affiliation: Department of Neurology, The Affiliated Hospital of Chifeng University, Chifeng 024000, Inner Mongolia, People's Republic of China.
authors.forename: Hong-Quan
authors.initials: HQ
authors.lastname: Wang
authors.forename: Yu-Xia
authors.initials: YX
authors.lastname: Xu
authors.forename: Cui-Qing
authors.initials: CQ
authors.lastname: Zhu
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005960:Glucosides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D010636:Phenols / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects; D059808:Polyphenols
chemical_list: D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; D005960:Glucosides; D051547:Heme Oxygenase-1; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; D010636:Phenols; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C058956:acteoside; D059808:Polyphenols