The effect of S-adenosylmethionine on CNS gene expression studied by cDNA microarray analysis

J Alzheimers Dis. 2006 Aug;9(4):415-9. doi: 10.3233/jad-2006-9407.

Abstract

High homocysteine (Hcy) together with low S-adenosylmethionine (SAM) levels are often observed in Alzheimer disease (AD), and this could be a sign of alteration of SAM/Hcy metabolism. It has already been shown that DNA methylation is involved in amyloid-beta-protein precursor (AbetaPP) processing and amyloid-beta(Abeta) production through the regulation of Presenilin 1 (PS1) expression and that exogenous SAM can silence the gene reducing Abeta. To investigate whether SAM administration globally influenced gene expression in the brain, we analysed 588 genes of the central nervous system in SK-N-BE neuroblastoma cells, with cDNA probes derived from untreated (DM; Differentiation Medium) or SAM treated (DM+SAM) cultures. In these conditions only seven genes were modulated by SAM treatment (and therefore by DNA methylation); three were up-regulated and four down-regulated, showing low levels of modulation.

MeSH terms

  • Aging
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics*
  • Amyloid beta-Protein Precursor / drug effects
  • Cell Line, Tumor / pathology
  • Chromatography, High Pressure Liquid
  • DNA Methylation / drug effects
  • Gene Expression / drug effects*
  • Humans
  • Membrane Proteins / drug effects
  • Membrane Proteins / metabolism
  • Neuroblastoma / metabolism
  • Neuroblastoma / pathology
  • Oligonucleotide Array Sequence Analysis / methods*
  • Presenilin-1
  • RNA / drug effects
  • RNA / genetics
  • RNA / metabolism
  • S-Adenosylmethionine / administration & dosage
  • S-Adenosylmethionine / pharmacology*
  • S-Adenosylmethionine / therapeutic use*

Substances

  • Amyloid beta-Protein Precursor
  • Membrane Proteins
  • PSEN1 protein, human
  • Presenilin-1
  • RNA
  • S-Adenosylmethionine