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Di(2-ethylhexyl) phthalate induces apoptosis through peroxisome proliferators-activated receptor-gamma and ERK 1/2 activation in testis of Sprague-Dawley rats.
- Source :
-
Journal of toxicology and environmental health. Part A [J Toxicol Environ Health A] 2007 Aug; Vol. 70 (15-16), pp. 1296-303. - Publication Year :
- 2007
-
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.
- Subjects :
- Administration, Oral
Animals
Apoptosis genetics
Diethylhexyl Phthalate pharmacology
Gene Expression drug effects
Male
Mitogen-Activated Protein Kinase 1 drug effects
Mitogen-Activated Protein Kinase 1 genetics
Mitogen-Activated Protein Kinase 1 metabolism
Mitogen-Activated Protein Kinase 3 drug effects
Mitogen-Activated Protein Kinase 3 genetics
Mitogen-Activated Protein Kinase 3 metabolism
PPAR gamma drug effects
PPAR gamma genetics
PPAR gamma metabolism
Plastics pharmacology
Rats
Rats, Sprague-Dawley
Scavenger Receptors, Class B drug effects
Scavenger Receptors, Class B genetics
Scavenger Receptors, Class B metabolism
Signal Transduction drug effects
Testis metabolism
Testis pathology
Apoptosis drug effects
Diethylhexyl Phthalate toxicity
Plastics toxicity
Testis drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1528-7394
- Volume :
- 70
- Issue :
- 15-16
- Database :
- MEDLINE
- Journal :
- Journal of toxicology and environmental health. Part A
- Publication Type :
- Academic Journal
- Accession number :
- 17654247
- Full Text :
- https://doi.org/10.1080/15287390701432160