Pravastatin inhibits pro-inflammatory effects of Alzheimer's peptide Abeta(1-42) in glioma cell culture in vitro

Pharmacol Res. 2003 Feb;47(2):119-26. doi: 10.1016/s1043-6618(02)00288-8.

Abstract

Statins are known to exert a number of biological effects apart from reducing cholesterol synthesis. The results of recent studies indicate that patients treated with pravastatin have a lower prevalence of diagnosed Alzheimer's disease (AD). These observations prompted us to examine the effects of pravastatin on Alzheimer's peptide (Abeta(1-42))-induced pro-inflammatory activation in the human glioma cell line in vitro. Cells alone or cells pre-treated with pravastatin (0.1mg x ml(-1)) for 24h were stimulated with 5 microM of freshly dissolved Abeta(1-42) for the next 24h. The pre-treatment of cells with pravastatin diminished the capacity of Abeta to induce metalloproteinases, cytokine IL-6 and free radical levels. Although both pravastatin and Abeta(1-42) separately increased PPARgamma activity, the combination of Abeta(1-42) and pravastatin resulted in no effect on PPARgamma expression. These data indicate that soluble forms of Abeta(1-42), which are a potent stimulus of pro-inflammatory activation of glioma cells in vitro, could be a good target for pravastatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / toxicity*
  • Brain Neoplasms / pathology*
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Colorimetry
  • Cytokines / biosynthesis
  • Electrophoresis, Polyacrylamide Gel
  • Electrophoretic Mobility Shift Assay
  • Free Radicals / metabolism
  • Glioma / pathology*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Inflammation / chemically induced*
  • Inflammation / prevention & control*
  • Lipid Peroxidation / drug effects
  • Matrix Metalloproteinase 9 / biosynthesis
  • Metalloendopeptidases / metabolism
  • Peptide Fragments / antagonists & inhibitors*
  • Peptide Fragments / toxicity*
  • Pravastatin / pharmacology*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Transcription Factors / metabolism
  • Tumor Cells, Cultured

Substances

  • Amyloid beta-Peptides
  • Cytokines
  • Free Radicals
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Peptide Fragments
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • amyloid beta-protein (1-42)
  • Metalloendopeptidases
  • Matrix Metalloproteinase 9
  • Pravastatin