Myelin is a preferential target of aluminum-mediated oxidative damage

Sandra V. Verstraeten, Mari S. Golub, Carl L Keen, Patricia I. Oteiza

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

The capacity of Al3+ to promote oxidative damage to brain membranes was investigated both in vitro and in vivo. In vitro, Al3+ and related metals (Sc3+, Ga3+, In3+, Be2+, Y3+, and La3+) stimulated Fe2+- initiated lipid and protein oxidation in brain myelin and synaptic membranes. Al3+, Sc3+, Y3+, and La3+ significantly promoted protein-associated carbonyl production in myelin, while in synaptic membranes, the stimulatory effect was observed in the presence of Ga3+, In3+, Y3+, Sc3+, and La3+. In myelin the magnitude of the stimulation of lipid oxidation followed the order Sc3+, Y3+, La3+ > Al3+, Ga3+, In3+ > Be3-. When compared to mitochondria and microsomal and synaptic membranes, myelin showed a marked susceptibility to Al3+-mediated lipid peroxidation. The differential susceptibility of myelin compared to synaptic membranes could not be explained by differences in membrane composition, since the relative content of negatively charged phospholipids (binding sites) was similar for both membranes, and myelin had a lower content of poly-unsaturated fatty acids (substrates of lipid oxidation) and a higher concentration of α- tocopherol compared to synaptic membranes. In a model of Al3+ intoxication imposed to mice during pregnancy and early development, a 72% higher content of lipid peroxidation products was found in brain myelin. The fluidity of myelin evaluated by the polarization fluorescence of 1,8-diphenylhexatriene was significantly higher in the Al3+-intoxicated mice than in controls. Since myelin has a high relative content of lipid:protein compared to other membranes, these results support our hypothesis that ions without redox capacity can stimulate in vitro and in vivo lipid oxidation by promoting phaseseparation and membrane rigidification, thus accelerating lipid oxidation.

Original languageEnglish (US)
Pages (from-to)289-294
Number of pages6
JournalArchives of Biochemistry and Biophysics
Volume344
Issue number2
DOIs
StatePublished - Aug 15 1997

Fingerprint

Myelin Sheath
Aluminum
Synaptic Membranes
Membranes
Lipids
Oxidation
Brain
Lipid Peroxidation
Diphenylhexatriene
Polyunsaturated fatty acids
Proteins
Fluorescence Polarization
Tocopherols
Mitochondria
Fluidity
Unsaturated Fatty Acids
Oxidation-Reduction
Phospholipids
Metals
Binding Sites

Keywords

  • Aluminum
  • Free radicals
  • Lipid peroxidation
  • Myelin
  • Neurotoxicity

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Myelin is a preferential target of aluminum-mediated oxidative damage. / Verstraeten, Sandra V.; Golub, Mari S.; Keen, Carl L; Oteiza, Patricia I.

In: Archives of Biochemistry and Biophysics, Vol. 344, No. 2, 15.08.1997, p. 289-294.

Research output: Contribution to journalArticle

Verstraeten, Sandra V. ; Golub, Mari S. ; Keen, Carl L ; Oteiza, Patricia I. / Myelin is a preferential target of aluminum-mediated oxidative damage. In: Archives of Biochemistry and Biophysics. 1997 ; Vol. 344, No. 2. pp. 289-294.
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