Peroxisome proliferator-activated receptor delta is a specific sensor for teratogenic valproic acid derivatives.
Eur J Pharmacol
; 431(1): 25-33, 2001 Nov 09.
Article
en En
| MEDLINE
| ID: mdl-11716839
ABSTRACT
The antiepileptic drug valproic acid (2-propylpentanoic acid) is a potent teratogen in both humans and mice. Valproic acid can induce differentiation of F9 teratocarcinoma cells and stimulate peroxisome proliferator-activated receptor (PPAR) activity. In this study, the structure-activity relationship between valproic acid, its teratogenic and non-teratogenic analogues (branched small- and medium chain fatty acids) and the three PPAR subtypes alpha, gamma or delta was investigated. PPAR-alpha and PPAR-gamma were activated by some valproic acid-derivatives; however, no correlation between teratogenicity and receptor activation could be observed. In contrast, only valproic acid and exclusively its teratogenic analogues were able to activate PPAR-delta in different cellular systems. However, valproic acid appears not to be a direct ligand of PPAR-delta, since in contrast to carbaprostacyclin (cPGI), valproic acid showed not to be able to induce complex formation of PPAR-delta-retinoid X receptor (RXR) heterodimers on DNA. In conclusion, in contrast to PPAR-alpha and PPAR-gamma, PPAR-delta shows to be a specific sensor for teratogenic valproic acid-derivatives.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Ácido Valproico
/
Receptores Citoplasmáticos y Nucleares
/
Anticonvulsivantes
Límite:
Animals
Idioma:
En
Revista:
Eur J Pharmacol
Año:
2001
Tipo del documento:
Article
País de afiliación:
Alemania