title: Amyloid beta-heme peroxidase promoted protein nitrotyrosination: relevance to widespread protein nitration in Alzheimer's disease.
abstract: Amyloid beta (Aβ) peptide accumulation has been demonstrated to play a central role in Alzheimer's disease (AD). Substantial evidence indicates that protein nitrotyrosination contributes to Aβ-dependent neurotoxicity; however, the molecular mechanism is unknown. Recent research has shown that Aβ complexes with heme to form Aβ-heme, and increases the pseudo-peroxidase activity of heme. We found that Aβ-heme uses H(2)O(2) and NO(2)(-) to cause nitration of enolase and synaptic proteins more effectively than heme. Thus, the increased peroxidase activity of Aβ-heme may be the molecular link between excess Aβ and the widespread protein nitration in AD. Interestingly, the site of enolase nitration that was catalyzed by Aβ-heme is different from that induced by heme. Moreover, the secondary structural perturbations of Aβ-heme-treated and heme-treated enolase are also different. These observations suggest that Aβ-heme targets specific amino acid sequences in enolase. Furthermore, our data show that Aβ-heme peroxidase activity is independent of the aggregation state of Aβ, suggesting an important role of soluble Aβ in addition to Aβ aggregates and oligomers in AD pathogenesis.
authors.affiliation: Department of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, People's Republic of China.
authors.forename: Can
authors.initials: C
authors.lastname: Yuan
authors.forename: Lian
authors.initials: L
authors.lastname: Yi
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yang
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Deng
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.forename: Hailing
authors.initials: H
authors.lastname: Li
authors.forename: Zhonghong
authors.initials: Z
authors.lastname: Gao
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D000682:Amyloid / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D006418:Heme / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009584:Nitrogen / Q000378:metabolism*; D009585:Nitrogen Dioxide / Q000378:metabolism; D010544:Peroxidases / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000378:metabolism
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D006418:Heme; D006861:Hydrogen Peroxide; D010544:Peroxidases; D010751:Phosphopyruvate Hydratase; D009584:Nitrogen; D009585:Nitrogen Dioxide