title: Astaxanthin upregulates heme oxygenase-1 expression through ERK1/2 pathway and its protective effect against beta-amyloid-induced cytotoxicity in SH-SY5Y cells.
abstract: Astaxanthin (ATX), the most abundant flavonoids in propolis, has been proven to exert neuroprotective property against glutamate-induced neurotoxicity and ischemia-reperfusion-induced apoptosis. Previous study have revealed that ATX can rescue PC12 cells from Aβ(25-35)-induced apoptotic death. However, the mechanisms by which ATX mediates its therapeutic effects in vitro are unclear. In the present study, we explored the underlying mechanisms involved in the protective effects of ATX on the Aβ(25-35)-induced cytotoxicity in SH-SY5Y cells. Pre-treatment with ATX for 4h significantly reduced the Aβ(25-35)-induced viability loss, apoptotic rate and attenuated Aβ-mediated ROS production. In addition, ATX inhibited Aβ(25-35)-induced lowered membrane potential, decreased Bcl-2/Bax ratio. We also demonstrated that ATX could prevent the activation of p38MAPK kinase pathways induced by Aβ. Moreover, we for the first time have revealed the ATX increased antioxidant enzyme heme oxygenase-1 (HO-1) expression in concentration-dependent and time-dependent manners, which were correlated with its protective effect against Aβ(25-35)-induced injury. Because the inhibitor of HO-1 activity, ZnPP reversed the protective effect of ATX against Aβ(25-35)-induced cell death. We also demonstrated that the specific ERK inhibitor, PD98059, concentration-dependently blocked on ATX-induced HO-1 expression, and meanwhile PD98059 reversed the protective effect of ATX against Aβ25-35-induced cell death. Taken together, these findings suggest that astaxanthin can induce HO-1 expression through activation of ERK signal pathways, thereby protecting the SH-SY5Y cells from Aβ(25-35)-induced oxidative cell death.
authors.affiliation: Shanghai Medical College, Fudan University, Shanghai 200032, People's Republic of China.
authors.forename: Hong-Quan
authors.initials: HQ
authors.lastname: Wang
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Sun
authors.forename: Yu-Xia
authors.initials: YX
authors.lastname: Xu
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: Qin-Yuan
authors.initials: QY
authors.lastname: Zhu
authors.forename: Cui-Qing
authors.initials: CQ
authors.lastname: Zhu
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000502:physiology*; D018696:Neuroprotective Agents; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D024341:Xanthophylls / Q000037:antagonists & inhibitors / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D051017:Apoptosis Regulatory Proteins; D005419:Flavonoids; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D024341:Xanthophylls; C089333:amyloid beta-protein (25-40); C005948:astaxanthine; D051547:Heme Oxygenase-1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D020782:Matrix Metalloproteinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one