Skip Navigation



ToxSci Advance Access published online on July 25, 2003
Toxicological Sciences, doi:10.1093/toxsci/kfg201
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
75/2/300    most recent
kfg201v1
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 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 arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Tharappel, J. C.
Right arrow Articles by Spear, B. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tharappel, J. C.
Right arrow Articles by Spear, B. T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received April 17, 2003; accepted July 14, 2003
© 2003 Society of Toxicology

Carcinogenicity

Cell Proliferation and Apoptosis Are Altered in Mice Deficient in the NF-{kappa}B p50 Subunit after Treatment with the Peroxisome Proliferator Ciprofibrate

Job C. Tharappel 1, Aysegul Nalca 2, Aaron B. Owens 3, Leila Ghabrial 2, Elizabeth C. Konz 4, Howard P. Glauert 5, and Brett T. Spear 6*

1 Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY; Graduate Center for Toxicology, University of Kentucky, Lexington, KY
2 Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, KY
3 Department of Nutrition and Food Science, University of Kentucky, Lexington, KY
4 Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY
5 Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY; Graduate Center for Toxicology, University of Kentucky, Lexington, KY; Department of Nutrition and Food Science, University of Kentucky, Lexington, KY
6 Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY; Graduate Center for Toxicology, University of Kentucky, Lexington, KY; Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, KY; Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, KY

* To whom correspondence should be addressed. E-mail: bspear{at}uky.edu.


  Abstract

We previously showed that the peroxisome proliferator ciprofibrate increases hepatic NF-{kappa}B DNA binding activity in rats, mice, and hepatoma cell lines. Here, we analyzed the response to ciprofibrate in mice that lack the NF-{kappa}B p50 gene (p50 -/-). Wild type and p50 -/- mice were fed a diet with or without 0.01% ciprofibrate for 10 days. NF-{kappa}B DNA binding activity was present and increased after ciprofibrate treatment in wild-type mice, but was not detected in p50 -/- mice. The untreated p50 -/- mice had a higher level of hepatic cell proliferation, as measured by BrdU labeling, than did untreated wild type mice. However, the increase in proliferation was greater in ciprofibrate-fed wild type mice than in ciprofibrate-fed p50 -/- mice. The apoptotic index was low in wild type mice in the presence or absence of ciprofibrate. Apoptosis was increased in untreated p50 -/- mice compared to wild type mice; apoptosis was reduced in p50 -/- mice after ciprofibrate feeding. The c-Jun and JunB mRNA levels were higher in untreated p50 -/- mice than in untreated control mice; c-Jun mRNA levels increased whereas JunB mRNA levels decreased in both groups after ciprofibrate treatment. c-Jun and JunB protein levels were the same in untreated wild-type and p50 -/- mice, and increased in both groups after ciprofibrate treatment. Several apoptosis-related mRNAs were higher in untreated p50 -/- mice compared to untreated control mice; expression of these genes increased in both groups after ciprofibrate treatment. These data indicate that NF-{kappa}B contributes to the proliferative and apoptotic changes that occur in the liver in response to ciprofibrate.

Key Words: Liver, NF-{kappa}B, Proliferation, Apoptosis, Peroxisome Proliferator, Ciprofibrate, Gene knock-out mice .


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


This article has been cited by other articles:


Home page
 Toxicol SciHome page
H. P. Glauert, A. Eyigor, J. C. Tharappel, S. Cooper, E. Y. Lee, and B. T. Spear
Inhibition of Hepatocarcinogenesis by the Deletion of the p50 Subunit of NF-{kappa}B in Mice Administered the Peroxisome Proliferator Wy-14,643
Toxicol. Sci., April 1, 2006; 90(2): 331 - 336.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
N. F. Cariello, E. H. Romach, H. M. Colton, H. Ni, L. Yoon, J. G. Falls, W. Casey, D. Creech, S. P. Anderson, G. R. Benavides, et al.
Gene Expression Profiling of the PPAR-alpha Agonist Ciprofibrate in the Cynomolgus Monkey Liver
Toxicol. Sci., November 1, 2005; 88(1): 250 - 264.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
Z. Lu, E. Y. Lee, L. W. Robertson, H. P. Glauert, and B. T. Spear
Effect of 2,2',4,4',5,5'-Hexachlorobiphenyl (PCB-153) on Hepatocyte Proliferation and Apoptosis in Mice Deficient in the p50 Subunit of the Transcription Factor NF-{kappa}B
Toxicol. Sci., September 1, 2004; 81(1): 35 - 42.
[Abstract] [Full Text] [PDF]


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.