科研之友
微信
新浪微博
Facebook
分享链接
摘要
It is known that copper ion (Cu(II)) binds to amyloid-beta peptide (A beta), induces A beta oligomer formation and ultimately exacerbates A beta-aggregation neurotoxicity in Alzheimer's disease (AD). It becomes interesting to know that how this chemical modification of A beta would affect interaction of A beta and Cu(II) and their roles in the development of AD. In this work, we investigated the interaction of A beta(1-42) nitration with the toxic Cu(II). It showed that Cu(II)induced A beta(1-42) nitration in the presence of nitrite and hydrogen peroxide. Circular dichroism studies also revealed significant conformational change of A beta(1-42) and Tyr10 nitrated amyloid-beta peptide(1-42) (A beta 1-42NT) when interacting with Cu(II). Even though nitration did not alter the binding of A beta(1-42) to Cu(II) or the peroxidative activity of A beta(1-42)-Cu(II) complex, nitration ameliorated the aggregation and neurotoxicity of A beta(1-42) induced by Cu(II), which was also further confirmed by the cell study. Given our previous findings that A beta nitration dramatically inhibited its aggregation and thus reduced its toxicity, we speculated that nitration of A beta(1-42) altered its intermolecular interaction, which protected itself against the toxicity of Cu(II). Based on this hypothesis, we propose that nitration of A beta(1-42) may be an important protective mechanism for normal function of A beta(1-42) and deserves more attention in AD drug development.
