Document Detail


Cellular defense mechanisms against benzo[a]pyrene in testicular Leydig cells: implications of p53, aryl-hydrocarbon receptor, and cytochrome P450 1A1 status.
MedLine Citation:
PMID:  17884947     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Leydig cells of the mammalian testis produce testosterone and support spermatogenesis, and thereby their role in male function is fundamental. Although benzo[a]pyrene (B[a]P) has been known to exhibit carcinogenic, apoptogenic, and endocrine-disrupting activities, its potential signaling system in Leydig cells remains to be discovered. In the present study, using the TM3 Leydig cell line and primary Leydig cells, we showed that Leydig cells do not die by exposure to B[a]P and found that an increased level of X chromosome-linked inhibitor of apoptosis protein may be associated with the antiapoptotic process. The Leydig cells were shown to express p53, but its translational level was extremely low. Although a high level of p53 protein was not necessary for apoptosis induced by B[a]P-7,8-diol-9,10-epoxide (a final B[a]P metabolite) in Leydig cells, the apoptosis of primary Leydig cells appears to be p53 independent. This indicates the lack of p53 function in primary Leydig cells. Furthermore, Leydig cells were found to retain insignificant levels of endogenous aryl-hydrocarbon receptor and AhR nuclear transporter proteins in nature. Exposure to B[a]P did not result in a significant increase in aryl-hydrocarbon receptor proteins that are required for CYP1A1 transcription. CYP1A1 expression was present in Leydig cells but at levels insufficient to exhibit its activity. Finally, we have demonstrated that overexpression of CYP1A1 in Leydig cells sensitizes the cells to exhibit its activity in the presence of B[a]P and, thus, induction of apoptosis. Together, these results indicate that the deficiency of CYP1A1 activity might be a decisive condition rendering Leydig cells secure from exogenous polycyclic aromatic hydrocarbons such as B[a]P.
Authors:
Jin-Yong Chung; Ji Young Kim; Yoon-Jae Kim; Sun Ju Jung; Ji-Eun Park; Seung Gee Lee; Jin Tac Kim; Seunghoon Oh; Chang Joo Lee; Yong-Dal Yoon; Young Hyun Yoo; Jong-Min Kim
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-09-20
Journal Detail:
Title:  Endocrinology     Volume:  148     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  2007 Dec 
Date Detail:
Created Date:  2007-11-16     Completed Date:  2008-06-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6134-44     Citation Subset:  AIM; IM    
Affiliation:
Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Dongdaeshin-dong 3-1, Seo-gu, Busan, Korea.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects
Aryl Hydrocarbon Receptor Nuclear Translocator / genetics,  metabolism
Benzo(a)pyrene / toxicity*
Blotting, Western
Cell Line
Cells, Cultured
Cytochrome P-450 CYP1A1 / genetics,  metabolism*
Immunohistochemistry
Leydig Cells / cytology,  drug effects*,  metabolism
Male
Mice
Phosphorylation / drug effects
Rats
Rats, Sprague-Dawley
Receptors, Aryl Hydrocarbon / genetics,  metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Testis / cytology
Tumor Suppressor Protein p53 / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Receptors, Aryl Hydrocarbon; 0/Tumor Suppressor Protein p53; 138391-32-9/Aryl Hydrocarbon Receptor Nuclear Translocator; 50-32-8/Benzo(a)pyrene; EC 1.14.14.1/Cytochrome P-450 CYP1A1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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