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-Delta(12.14)-prostaglandin I-2 (15-deoxy PGI(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-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 mug/ml) and/or 15-deoxy PGI(2) (0.5 muM) 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 PGI(2). OTA caused concentration-dependent reductions in neurite outgrowth and cell number, and induced AP-1 and NF-kappaB activation. Cotreatment with 15-deoxy, PGI(2) (0.5 muM) blocked OTA-induced decrease in neurite outgrowth and cell number and inhibited AP-1 and NF-kappaB activation, 15-Deoxy PGI(2) (0.5 muM) caused the expression of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in the cells, Results show that 15-deoxy PGI(2) blocked OTA-induced neurotoxicity by inhibiting AP-1 and NF-kappaB activation in cultured rat embryonic midbrain cells.