High cholesterol diet down regulates the activity of activator protein-1 but not nuclear factor-kappa B in rabbit brain

János Kálmán, Bhalchandra J. Kudchodkar, Raghu Krishnamoorthy, Ladislav Dory, Andras G. Lacko, Neeraj Agarwal

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Cardiovascular risk factors and alterations in cholesterol metabolism are implicated in the pathogenesis of Alzheimer's dementia (AD). The hypercholesterolemic rabbit model of atheroslerosis and AD was utilized in this study to examine oxidative stress related changes in the brain. The high cholesterol diet induced dramatic increases in plasma and liver cholesterol concentrations, but brain cholesterol levels remained constant. Similar effects have been found regarding lipid oxidation products. The amounts of conjugated dienes, trienes and thiobarbituric acid reactive substances (TBARS) significantly increased in the plasma of cholesterol treated animals while the brain cortex showed no signs of increased lipid peroxidation. The oxidative damage sensitive nuclear transcription factor kappa B (NF-κB) and activator protein-1 (AP-1) diverged in their responses. Accordingly, the AP-1 DNA binding activity decreased by more than 50% in brain nuclear protein extracts while the NF-κB binding activity remained unaltered by the hypercholesterol diet. These results indicate that despite the relative resistance of the central nervous system to dietary manipulation of its lipid composition and lipid peroxidation products, chronic dietary intake of cholesterol can alter the function of certain proteins involved in regulation of gene expression in the brain.

Original languageEnglish
Pages (from-to)1495-1503
Number of pages9
JournalLife Sciences
Volume68
Issue number13
DOIs
StatePublished - 16 Feb 2001

Keywords

  • Cholesterol diet
  • Effect on brain transcription factors and lipid peroxidation

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