Protective role of heme oxygenase-1 in oxidative stress-induced neuronal injury.
Heme oxygenase-1 (HO-1) is a stress protein induced in response to a variety of oxidative challenges. After treatment of the hybrid septal cells SN 56 with beta-amyloid peptide (beta-AP1-40) or hydrogen peroxide (H2O2), we detected high levels of reactive oxygen species, accompanied by a significant elevation in HO-1 expression. Levels of HO-1 increased and then decreased following cell loss. Pretreatment of SN 56 cells with HO-1 antisense oligonucleotides dramatically decreased the immunoreactivity of HO-1 and significantly enhanced the cytotoxicity of beta-AP1-40 and H2O2. In contrast, pretreatment with hemin, an HO-1 inducer, increased the expression of HO-1 and decreased the beta-AP1-40- and H2O2-induced cytotoxicity. These findings support the importance of HO-1 in protecting neurons against oxidative stress-induced injury.
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Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USA. Weidongl@bcm.tmc.edu
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D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006427:Hemin / Q000494:pharmacology; D006822:Hybrid Cells; D006861:Hydrogen Peroxide / Q000633:toxicity; D007700:Kinetics; D008565:Membrane Proteins; D051379:Mice; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology*; D010446:Peptide Fragments / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D013873:Thionucleotides; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D008565:Membrane Proteins; D009838:Oligodeoxyribonucleotides; D020319:Oligodeoxyribonucleotides, Antisense; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D013873:Thionucleotides; C078592:amyloid beta-protein (1-40); D006427:Hemin; D006861:Hydrogen Peroxide; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse