Inhibitory effect of peroxisome proliferator-activated receptor gamma agonist on ochratoxin A-induced cytotoxicity and activation of transcription factors in cultured rat embryonic midbrain cells

J Toxicol Environ Health A. 2002 Mar;65(5-6):407-18. doi: 10.1080/15287390252808073.

Abstract

The effects of 15-deoxy-delta12,14-prostaglandin J2 (15-deoxy PGJ2) on ochratoxin A (OTA)-induced neurotoxicity and on the activation of transcription factors activator protein-1 (AP-1) and nuclear factor-kappa B (NF-kappaB) were investigated in cultured rat embryonic midbrain cells. Twelve-day rat embryo midbrain cells were cultured for 48 h. OTA (0.5 or 1 microg/ml) and/or 1.5-deoxy PGJ2 (0.5 microM) were then added for 48 h. Cell number and neurite outgrowth were determined to assess the neurotoxicity of OTA. AP-1 and NF-kappaB activation was determined by gel mobility shift assay after 3 h of exposure to OTA and/or 15-deoxy PGI2. OTA caused concentration-dependent reductions in neurite outgrowth and cell number, and induced AP-1 and NF-kappaB activation. Cotreatment with 15-deoxy PGJ2 (0..5 microM) blocked OTA-induced decrease in neurite outgrowth and cell number and inhibited AP-1 and NF-kappaB activation. 15-Deoxy PGJ2 (0.5 microM) caused the expression of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in the cells. Results show that 1.5-deoxy PGJ2 blocked OTA-induced neurotoxicity by inhibiting AP-1 and NF-kappaB activation in cultured rat embryonic midbrain cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogens / toxicity*
  • Cell Culture Techniques
  • Cell Division
  • Drug Interactions
  • Immunologic Factors / pharmacology*
  • Mesencephalon / cytology
  • Mesencephalon / embryology
  • NF-kappa B / biosynthesis
  • Neurites / drug effects
  • Ochratoxins / toxicity*
  • Prostaglandin D2 / analogs & derivatives*
  • Prostaglandin D2 / pharmacology*
  • Rats
  • Transcription Factor AP-1 / biosynthesis*
  • Transcription Factor AP-1 / pharmacology

Substances

  • 15-deoxy-delta(12,14)-prostaglandin J2
  • Carcinogens
  • Immunologic Factors
  • NF-kappa B
  • Ochratoxins
  • Transcription Factor AP-1
  • ochratoxin A
  • Prostaglandin D2