Oxidation of methionine 35 reduces toxicity of the amyloid beta-peptide(1-42) in neuroblastoma cells (IMR-32) via enzyme methionine sulfoxide reductase A expression and function.

Bruno Giardina, Francesco Misiti, Maria Elisabetta Clementi

Risultato della ricerca: Contributo in rivistaArticolo in rivista

31 Citazioni (Scopus)

Abstract

The beta amyloid peptide (A beta), the major protein component of brain senile plaques in Alzheimer's disease, is known to be directly responsible for the production of free radicals that may lead to neurodegeneration. Our recent evidence suggest that the redox state of methionine residue in position 35 (Met-35) of A beta has the ability to deeply modify peptide's neurotoxic actions. Reversible oxidation of methionine in proteins involving the enzyme methionine sulfoxide reductase type A (MsrA) is postulated to serve a general antioxidant role and a decrease in MsrA has been implicated in Alzheimer's disease. In rat neuroblastoma cells (IMR-32), we used A beta(1-42), in which the Met-35 is present in the reduced state, with a modified peptide with oxidized Met-35 (A beta(1-42)Met35(ox)), as well as an A beta-derivative in which Met-35 is substituted with norleucine (A beta(1-42)Nle35) to investigate the relationship between Met-35 redox state, expression and function of MsrA and reactive oxygen species (ROS) generation. The obtained results shown that MsrA activity, as well as mRNA levels, increase in IMR-32 cells treated with A beta(1-42)Met35(ox), differently to that shown by the reduced derivative. The increase in MsrA function and expression was associated with a decline of ROS levels. None of these effects were observed when cells were exposed to A beta containing oxidized Met35 (A beta 1-42)Met35(ox). Taken together, the results of the present study indicate that the differential toxicity of A beta peptides containing reduced or oxidised Met-35 depends on the ability of the latter form to reduce ROS generation by enhancing MsrA gene expression and function and suggests the therapeutic potential of MsrA in Alzheimer's disease
Lingua originaleEnglish
pagine (da-a)597-602
Numero di pagine6
RivistaNeurochemistry International
Volume56
Stato di pubblicazionePubblicato - 2010

Keywords

  • Alzheimer's disease
  • Amyloid beta-peptide (A beta(1-42))
  • Methionine
  • ROS

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