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

Abstract

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/H 2 O 2 / NO -system by immunohistochemical staining, and the oxide mediated modification of serum transthyretin (TTR) was observed upon exposure to the MPO/H 2 O 2 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/H 2 O 2 /NO -system. Nitric oxide-mediated modification of TTR may play a role in

Reactive Vasodilation Predicts Mortality in Primary Systemic Light-Chain Amyloidosis

“…52 Although there are no specific data in AL, in other β-sheet amyloidosis such as Aβ (amyloid-β) deposition and transthyretin amyloidosis, nitrosylation of tyrosine may be directly involved in disease pathogenesis. 53–55 Thus, our unexpected observation of increased NTY levels in high-risk AL patients with elevated FMD may reflect a parallel disease processes with nitrotyrosine being involved in amyloidosis progression. On the contrary, recent experimental evidence indicates that nitrotyrosine may induce unexpected vasodilatory response to β-adrenergic agonists through blocking of β2 adrenergic receptor internalization at nerve endings.…”