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-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.
Hong
Jin Tae
JT
College of Pharmacy, Chungbuk National University, Korea.
Lee
Myung Koo
MK
Park
Ki Sook
KS
Jung
Kyung Mi
KM
Lee
Rhee Da
RD
Jung
Hai Kwan
HK
Park
Kui Lae
KL
Yang
Ki Jwa
KJ
Chung
Youn Soo
YS
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
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