Effect of nitric oxide in amyloid fibril formation on transthyretin-related amyloidosis

Shiori Saito, Yukio Ando, Masaaki Nakamura, Mitsuharu Ueda, Jaemi Kim, Yu Ishima, Takaaki Akaike, Masaki Otagiri

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)


Although oxidative stress is said to play an important role in the amyloid formation mechanism in several types of amyloidosis, few details about this role have been described. Amyloid is commonly deposited around the vessels that are the primary site of action of nitric oxide generated from endothelial cells and smooth muscle cells, so nitric oxide may be also implicated in amyloid formation. For this study, we examined the in vitro effect of S-nitrosylation on amyloid formation induced by wild-type transthyretin, a precursor protein of senile systemic amyloidosis, and amyloidogenic transthyretin V30M, a precursor protein of amyloid deposition in familial amyloidotic polyneuropathy. S-Nitrosylation of amyloidogenic transthyretin V30M via the cysteine at position 10 was 2 times more extensive than that of wild-type transthyretin in a nitric oxide-generating solution. Both wild-type transthyretin and amyloidogenic transthyretin V30M formed amyloid fibrils under acidic conditions, and S-nitrosylated transthyretins exhibited higher amyloidogenicity than did unmodified transthyretins. Moreover, S-nitrosylated amyloidogenic transthyretin V30M formed more fibrils than did 5-nitrosylated wild-type transthyretin. Structural studies revealed that S-nitrosylation of amyloidogenic transthyretin V30M induced a change in its conformation, as well as instability of the tetramer conformation. These results suggest that the nitric oxide-mediated modification of transthyretin, especially variant transthyretin, may play an important role in amyloid formation in senile systemic amyloidosis and familial amyloidotic polyneuropathy.

Original languageEnglish
Pages (from-to)11122-11129
Number of pages8
Issue number33
Publication statusPublished - 2005 Aug 23
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry


Dive into the research topics of 'Effect of nitric oxide in amyloid fibril formation on transthyretin-related amyloidosis'. Together they form a unique fingerprint.

Cite this