Skip Navigation


ToxSci Advance Access originally published online on February 16, 2005
Toxicological Sciences 2005 85(1):585-593; doi:10.1093/toxsci/kfi118
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
85/1/585    most recent
kfi118v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (5)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Kim, J.-H.
Right arrow Articles by Baek, S. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kim, J.-H.
Right arrow Articles by Baek, S. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Toxicological Sciences vol. 85 no. 1 © The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org

Evaluation of Polycyclic Aromatic Hydrocarbons in the Activation of Early Growth Response-1 and Peroxisome Proliferator Activated Receptors

Jeong-Ho Kim*, Kiyoshi Yamaguchi*, Seong-Ho Lee*, Patricia K. Tithof*, Gary S. Sayler{dagger}, Joo-Heon Yoon{ddagger} and Seung Joon Baek*,1

* Department of Pathobiology, and {dagger} Department of Microbiology, University of Tennessee, Knoxville, Tennessee 37996, and {ddagger} Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, South Korea

Received December 6, 2004; accepted February 9, 2005

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental and food contaminants with known or suspected carcinogenic properties. In this study, we have evaluated whether PAHs activate the early growth response (EGR-1) gene and bind to peroxisome proliferator-activated receptor alpha (PPAR{alpha}) and delta (PPARß/{delta}) in cell culture systems. Luciferase reporter systems were employed and several PAHs were evaluated for their ability to activate EGR-1 and PPARs. Some PAHs enhanced EGR-1 expression and activated PPAR{alpha} and PPARß. Among them, benz(a)anthracene was found to act as a relatively potent activator of PPAR{alpha} and PPARß/{delta}, and to significantly enhance EGR-1 transcription. These in vitro assays were confirmed by Western blot analysis, using cell lysates of tissue samples from mouse trapped at a highly contaminated Superfund site in the Chattanooga Creek floodplain in Chattanooga, Tennessee. We have found that a PPAR target gene, glycogen synthase kinase-3ß (GSK-3ß), was down-regulated and EGR-1 was up-regulated in the mouse samples of Chattanooga Creek. In addition, select PAHs repressed GSK-3ß and induced CYP4A in FaO rat hepatoma cells. In conclusion, PAHs activate PPAR{alpha} and PPARß/{delta}, and up-regulate EGR-1 expression in vitro as well as in vivo. These data may provide a diversity of PAH activity in several biological pathways.

Key Words: PAHs; PPAR{alpha}; PPAR{delta}; EGR-1; GSK-3ß.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.