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Nitration and oligomerization of tau induced by peroxynitrite inhibit its microtubule‐binding activity
Author(s) -
Zhang Yong Jie,
Xu Ya Fei,
Chen Xiao Qian,
Wang Xiao Chuan,
Wang Jian-Zhi
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.03.041
Subject(s) - peroxynitrite , nitration , chemistry , neurodegeneration , microtubule , in vitro , biochemistry , tau protein , tubulin , biophysics , microbiology and biotechnology , alzheimer's disease , biology , enzyme , pathology , disease , medicine , organic chemistry , superoxide
Abnormally nitrated tau has been found recently in the neurofibrillary tangles of Alzheimer's disease (AD). However, whether and how nitration of tau is involved in AD pathology is not known. Herein, we found that in vitro incubation of peroxynitrite with recombinant tau resulted in nitration and oligomerization of tau in a dosage‐dependent manner. Moreover, the nitrated tau showed a significantly decreased binding activity to taxol‐stabilized microtubulesin in vitro. Further study demonstrated that peroxynitrite also induced tau nitration in neuroblastoma N2a cell line, and the nitrated tau was accumulated in the cells. We conclude that abnormal nitration of tau contributes to the impaired biological activity of tau in binding to the microtubules and the aggregation of tau, implying a novel mechanism responsible for the neurodegeneration seen in AD brain.