Nitration of Y10 in Aβ1-40: is it a compensatory reaction against oxidative/nitrative stress and Aβ aggregation?
Amyloid β peptide (Aβ) aggregation is considered to be a crucial pathological biomarker of Alzheimer's disease (AD). It was found that Aβ and heme can form an Aβ-heme complex, which results in increased heme pseudoperoxidase activity. Recently, we found that increasing pseudoperoxidase activity induces elevated tyrosine nitration on Aβ in the presence of nitrite and hydrogen peroxide. However, the nature of tyrosine nitration of Aβ and its physiologic significance are still unknown. In this study, we revealed that Aβ1-40 can be nitrated in vitro by binding to heme in the presence of nitrite and hydrogen peroxide. Moreover, we found that tyrosine nitration had little effect on Aβ1-40's binding activity with heme. A TMB assay also revealed that the peroxidase activity of the heme-Aβ1-40Y10(3N)T (tyrosine 10 was replaced with 3-nitrtotyrosine in Aβ1-40) complex was moderately increased compared with that of the heme-Aβ1-40 complex. Furthermore, Thioflavin T fluorescence and transmission electron microscopic characterization indicated that tyrosine nitration significantly decreased the aggregation of Aβ1-40. In addition, a cytotoxicity test verified that wild-type Aβ1-40 was more cytotoxic than that of Aβ1-40Y10(3N)T. These results suggest that nitration of Aβ1-40 might be an Aβ detoxicant process and a compensatory reaction to nitrative stress. Our findings may lead to a detailed understanding of the function of Aβ1-40 and may be helpful in preventing and curing AD.
School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology , Wuhan 430074, People's Republic of China.
Jie
J
Zhao
Peipei
P
Wang
Hailing
H
Li
Zhonghong
Z
Gao
D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006418:Heme / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism*; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D010544:Peroxidases / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D014443:Tyrosine / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D009573:Nitrites; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D014443:Tyrosine; D006418:Heme; D006861:Hydrogen Peroxide; D010544:Peroxidases