Alpha-synuclein can function as an antioxidant preventing oxidation of unsaturated lipid in vesicles

Biochemistry. 2006 Jul 4;45(26):8135-42. doi: 10.1021/bi052584t.

Abstract

Alpha-synuclein, a presynaptic protein associated with Parkinson's disease, is found as both soluble cytosolic and membrane-bound forms. Although the function of alpha-synuclein is unknown, several observations suggest that its association with membranes is important. In the present study we investigated the effect of alpha-synuclein on lipid oxidation in membranes containing phospholipids with unsaturated fatty acids. The kinetics of lipid oxidation were monitored by the change in fluorescence intensity of the dye C11-BODIPY. We find that monomeric alpha-synuclein efficiently prevented lipid oxidation, whereas fibrillar alpha-synuclein had no such effect. Our data suggest that the prevention of unsaturated lipid oxidation by alpha-synuclein requires that it bind to the lipid membrane. The antioxidant function of alpha-synuclein is attributed to its facile oxidation via the formation of methionine sulfoxide, as shown by mass spectrometry. These findings suggest that the inhibition of lipid oxidation by alpha-synuclein may be a physiological function of the protein.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antioxidants / metabolism*
  • Boron Compounds
  • Circular Dichroism
  • Fluorescence
  • Kinetics
  • Liposomes*
  • Oxidation-Reduction
  • Phosphatidylcholines
  • Phosphatidylglycerols
  • alpha-Synuclein / chemistry
  • alpha-Synuclein / isolation & purification
  • alpha-Synuclein / metabolism*

Substances

  • 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
  • Antioxidants
  • Boron Compounds
  • Liposomes
  • Phosphatidylcholines
  • Phosphatidylglycerols
  • alpha-Synuclein
  • 1-palmitoyl-2-oleoylglycero-3-phosphoglycerol
  • 1-palmitoyl-2-oleoylphosphatidylcholine