α-Synuclein-mediated defense against oxidative stress via modulation of glutathione peroxidase

Biochim Biophys Acta. 2013 Jun;1834(6):972-6. doi: 10.1016/j.bbapap.2013.03.008. Epub 2013 Mar 16.

Abstract

In this report, mutual effect of α-synuclein and GPX-1 is investigated to unveil their involvement in the PD pathogenesis in terms of cellular defense mechanism against oxidative stress. Biochemical and immunocytochemical studies showed that α-synuclein enhanced the GPX-1 activity with Kd of 17.3nM and the enzyme in turn markedly enhanced in vitro fibrillation of α-synuclein. Transmission electron microscopy revealed the fibrillar meshwork of α-synuclein containing GPX-1 located in locally concentrated islets. The entrapped enzyme was demonstrated to be protected in a latent form and its activity was fully recovered as released from the matrix. Therefore, novel defensive roles of α-synuclein and its amyloid fibrils against oxidative stress are suggested as the GPX-1 stimulator and the active depot for the enzyme, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / metabolism
  • Animals
  • Antioxidants / metabolism
  • Cattle
  • Glutathione Peroxidase / metabolism*
  • Glutathione Peroxidase GPX1
  • Humans
  • Oxidative Stress / physiology*
  • Parkinson Disease / metabolism
  • Recombinant Proteins / metabolism
  • alpha-Synuclein / metabolism*

Substances

  • Amyloid
  • Antioxidants
  • Recombinant Proteins
  • alpha-Synuclein
  • Glutathione Peroxidase
  • Glutathione Peroxidase GPX1