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.

The effects of 15-deoxy- j 12,14 -prostaglandin J 2 (15-deoxy PGJ 2 ) on ochratoxin A (OTA)-induced neurotoxicity and on the activation of transcription factors activator protein-1 (AP-1) and nuclear factor-kappa B (NF- s B) were investigated in cultured rat embryonic midbrain cells. Twelve-day rat embryo midbrain cells were cultured for 48 h. OTA (0.5 or 1 µg/ml) and/or 15-deoxyPGJ 2 (0.5 µ M ) were then added for 48 h. Cell number and neurite outgrowth were determined to assess the neurotoxicity of OTA. AP-1 and NF- s B activation was determined by gel mobility shift assay after 3 h of exposure to OTA and/or 15-deoxy PGJ 2 . OTA caused concentration-dependent reductions in neurite outgrowth and cell number, and induced AP-1 and NF- s B activation. Cotreatment with 15-deoxy PGJ 2 (0.5 µ M ) blocked OTA-induced decrease in neurite outgrowth and cell number and inhibited AP-1 and NF- s B activation. 15-Deoxy PGJ 2 (0.5 µ M ) caused the expression of peroxisome proliferator-activated receptor-gamma (PPAR- n...