Research Article

Effect of MPO/H2O2/NO- system on nitric oxide-mediated modification of TTR amyloid and serum TTR in FAP ATTR Val30Met patients

Published: April 03, 2014
Genet. Mol. Res. 13 (2) : 2368-2376 DOI: 10.4238/2014.April.3.9

Abstract

Amyloid deposits consist of protein fibrils and amorphous material, and this deposition is related to oxidative stress. Previously, we demonstrated the presence of high-density lipoproteins and/or lipids in amyloid deposits of familial amyloid polyneuropathy patients. In this study, the presence of myeloperoxidase (MPO) in amyloid deposits was demonstrated using immunohistochemical staining. In contrast, normal surrounding tissues were consistently negative for MPO. Nitrotyrosine was present in amyloid deposits after being exposed to the MPO/H2O2/NO- system by immunohistochemical staining, and the oxide mediated modification of serum transthyretin (TTR) was observed upon exposure to the MPO/H2O2 system using two-dimensional gel electrophoresis and TTR Western blotting. This observation revealed that the TTR amyloid deposits and serum TTR were oxidized by the MPO/H2O2/NO- system. Nitric oxide-mediated modification of TTR may play a role in amyloidogenesis in vivo.

Amyloid deposits consist of protein fibrils and amorphous material, and this deposition is related to oxidative stress. Previously, we demonstrated the presence of high-density lipoproteins and/or lipids in amyloid deposits of familial amyloid polyneuropathy patients. In this study, the presence of myeloperoxidase (MPO) in amyloid deposits was demonstrated using immunohistochemical staining. In contrast, normal surrounding tissues were consistently negative for MPO. Nitrotyrosine was present in amyloid deposits after being exposed to the MPO/H2O2/NO- system by immunohistochemical staining, and the oxide mediated modification of serum transthyretin (TTR) was observed upon exposure to the MPO/H2O2 system using two-dimensional gel electrophoresis and TTR Western blotting. This observation revealed that the TTR amyloid deposits and serum TTR were oxidized by the MPO/H2O2/NO- system. Nitric oxide-mediated modification of TTR may play a role in amyloidogenesis in vivo.