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

• Published in: Journal of Toxicology and Environmental Health, Part A Part A, 2002-03, Vol.65 (5-6), p.407-418
• Main Authors: Hong, Jin Tae, Lee, Myung Koo, Park, Ki Sook, Jung, Kyung Mi, Lee, Rhee Da, Jung, Hai Kwan, Park, Kui Lae, Yang, Ki Hwa, Chung, Soo Youn
• Format: Article
• Language: English
• Subjects: Animals; Carcinogens - toxicity; Cell Culture Techniques; Cell Division; Drug Interactions; Immunologic Factors - pharmacology; Mesencephalon - cytology; Mesencephalon - embryology; Neurites - drug effects; NF-kappa B - biosynthesis; Ochratoxins - toxicity; Prostaglandin D2 - analogs & derivatives; Prostaglandin D2 - pharmacology; Rats; Transcription Factor AP-1 - biosynthesis; Transcription Factor AP-1 - pharmacology
• ISSN: 1528-7394; 1087-2620
• DOI: 10.1080/15287390252808073

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 ) in the cells. Results show that 15-deoxy PGJ 2 blocked OTA-induced neurotoxicity by inhibiting AP-1 and NF- s B activation in cultured rat embryonic midbrain cells.