title: 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.
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.
authors.affiliation: College of Pharmacy, Chungbuk National University, Korea.
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
authors.forename: Myung Koo
authors.initials: MK
authors.lastname: Lee
authors.forename: Ki Sook
authors.initials: KS
authors.lastname: Park
authors.forename: Kyung Mi
authors.initials: KM
authors.lastname: Jung
authors.forename: Rhee Da
authors.initials: RD
authors.lastname: Lee
authors.forename: Hai Kwan
authors.initials: HK
authors.lastname: Jung
authors.forename: Kui Lae
authors.initials: KL
authors.lastname: Park
authors.forename: Ki Jwa
authors.initials: KJ
authors.lastname: Yang
authors.forename: Youn Soo
authors.initials: YS
authors.lastname: Chung
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D018929:Cell Culture Techniques; D002455:Cell Division; D004347:Drug Interactions; D007155:Immunologic Factors / Q000494:pharmacology*; D008636:Mesencephalon / Q000166:cytology / Q000196:embryology; D016328:NF-kappa B / Q000096:biosynthesis; D016501:Neurites / Q000187:drug effects; D009793:Ochratoxins / Q000633:toxicity*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D018808:Transcription Factor AP-1 / Q000096:biosynthesis* / Q000494:pharmacology
chemical_list: C097240:15-deoxy-delta(12,14)-prostaglandin J2; D002273:Carcinogens; D007155:Immunologic Factors; D016328:NF-kappa B; D009793:Ochratoxins; D018808:Transcription Factor AP-1; C025589:ochratoxin A; D015230:Prostaglandin D2