Di(2-ethylhexyl) phthalate induces apoptosis through peroxisome proliferators-activated receptor-gamma and ERK 1/2 activation in testis of Sprague-Dawley rats.
J Toxicol Environ Health A
; 70(15-16): 1296-303, 2007 Aug.
Article
em En
| MEDLINE
| ID: mdl-17654247
ABSTRACT
Di(2-ethylhexyl) phthalate (DEHP) is a well-known hepatic and reproductive toxicant whose toxicity may be mediated by peroxisome proliferators-activated receptor (PPAR). This study examined the effects of DEHP on the expression of PPAR-regulated genes involved in testicular cells apoptosis. Sprague-Dawley male rats were treated orally with 250, 500, or 750 mg/kg/d DEHP for 28 d, while control rats were given corn oil. The levels of cell cycle regulators (pRb, cyclins, CDKs, and p21) and apoptosis-related proteins were analyzed by Western blot analysis. The role of PPAR-gamma (PPAR-gamma), class B scavenger receptor type 1 (SR-B1), and ERK1/2 was further studied to examine the signaling pathway for DEHP-induced apoptosis. Results showed that the levels of pRB, cyclin D, CDK2, cyclin E, and CDK4 were significantly lower in rats given 500 and 750 mg/kg/d DEHP, while levels of p21 were significantly higher in rat testes. Dose-dependent increases in PPAR-gamma and RXRalpha proteins were observed in testes after DEHP exposure, while there was a significant decrease in RXRgamma protein levels. In addition to PPAR-gamma, DEHP also significantly increased SR-B1 mRNA and phosphorylated ERK1/2 protein levels. Furthermore, DEHP treatment induced pro-caspase-3 and cleavage of its substrate protein, poly(ADP-ribose) polymerase (PARP), in a dose-dependent manner. Data suggest that DEHP exposure may induce the expression of apoptosis-related genes in testes through induction of PPAR-gamma and activation of the ERK1/2 pathway.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plásticos
/
Testículo
/
Apoptose
/
Dietilexilftalato
Limite:
Animals
Idioma:
En
Revista:
J Toxicol Environ Health A
Assunto da revista:
SAUDE AMBIENTAL
/
TOXICOLOGIA
Ano de publicação:
2007
Tipo de documento:
Article