|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 279, Issue 50, 52390-52398, December 10, 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
The Transcriptional Response to a Peroxisome Proliferator-activated Receptor 
Agonist Includes Increased Expression of Proteome Maintenance Genes*
From the
Investigative Toxicology and Pathology Group, Safety Assessment, GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina 27709, ¶Experimental Pathology Laboratories Inc., Research Triangle Park, North Carolina 27709, ||CIIT Centers for Health Research, Research Triangle Park, North Carolina 27709, **NCI-NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, BASF AG, Ludwigshafen, 67056 Germany, the Department of Environmental Health Sciences, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, 21205 and ¶¶ToxicoGenomics, Chapel Hill, North Carolina 27514
The nuclear receptor peroxisome proliferator-activated receptor 
(PPAR), in addition to regulating lipid homeostasis, controls the level of tissue damage after chemical or physical stress. To determine the role of PPAR in oxidative stress responses, we examined damage after exposure to chemicals that increase oxidative stress in wild-type or PPAR-null mice. Primary hepatocytes from wild-type but not PPAR-null mice pretreated with the PPAR pan-agonist WY-14,643 (WY) were protected from damage to cadmium and paraquat. The livers from intact wild-type but not PPAR-null mice were more resistant to damage after carbon tetrachloride treatment. To determine the molecular basis of the protection by PPAR, we identified by transcript profiling genes whose expression was altered by a 7-day exposure to WY in wild-type and PPAR-null mice. Of the 815 genes regulated by WY in wild-type mice (p 
0.001; 
1.5-fold or -1.5-fold), only two genes were regulated similarly by WY in PPAR-null mice. WY increased expression of stress modifier genes that maintain the health of the proteome, including those that prevent protein aggregation (heat stress-inducible chaperones) and eliminate damaged proteins (proteasome components). Although the induction of proteasomal genes significantly overlapped with those regulated by 1,2-dithiole-3-thione, an activator of oxidant-inducible Nrf2, WY increased expression of proteasomal genes independently of Nrf2. Thus, PPAR controls the vast majority of gene expression changes after exposure to WY in the mouse liver and protects the liver from oxidant-induced damage, possibly through regulation of a distinct set of proteome maintenance genes.
Received for publication, August 16, 2004 , and in revised form, September 15, 2004.
* This work was supported by NIEHS, National Institutes of Health, Grant ES09775-01 (to J. C. C.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The on-line version of this article (available at http://www.jbc.org) contains two additional figures and tables.
Present address: Bayer Corp., 85 T. W. Alexander Dr., Research Triangle Park, NC 27709.
|||| To whom correspondence and reprint requests should be addressed: ToxicoGenomics, 209 Silver Creek Tr., Chapel Hill, NC 27514. Tel.: 919-801-0887; Fax: 919-408-0365; E-mail: ccorton{at}msn.com.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  U. Bernabucci, L. Basirico, P. Morera, N. Lacetera, B. Ronchi, and A. Nardone Heat shock modulates adipokines expression in 3T3-L1 adipocytes J. Mol. Endocrinol., February 1, 2009; 42(2): 139 - 147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D. Kane, K. A. Stevens, J. E. Fischer, M. Haghpassand, L. J. Royer, C. Aldinger, K. T. Landschulz, P. Zagouras, S. W. Bagley, W. Hada, et al. Molecular Characterization of Novel and Selective Peroxisome Proliferator-Activated Receptor {alpha} Agonists with Robust Hypolipidemic Activity in Vivo Mol. Pharmacol., February 1, 2009; 75(2): 296 - 306. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Maher, L. M. Aleksunes, M. Z. Dieter, Y. Tanaka, J. M. Peters, J. E. Manautou, and C. D. Klaassen Nrf2- and PPAR{alpha}-Mediated Regulation of Hepatic Mrp Transporters after Exposure to Perfluorooctanoic Acid and Perfluorodecanoic Acid Toxicol. Sci., December 1, 2008; 106(2): 319 - 328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Nishimura, Y. Dewa, T. Okamura, M. Jin, Y. Saegusa, M. Kawai, T. Umemura, M. Shibutani, and K. Mitsumori Role of Nrf2 and Oxidative stress on Fenofibrate-Induced Hepatocarcinogenesis in Rats Toxicol. Sci., December 1, 2008; 106(2): 339 - 349. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. Rosen, J. S. Lee, H. Ren, B. Vallanat, J. Liu, M. P. Waalkes, B. D. Abbott, C. Lau, and J. C. Corton Toxicogenomic Dissection of the Perfluorooctanoic Acid Transcript Profile in Mouse Liver: Evidence for the Involvement of Nuclear Receptors PPAR{alpha} and CAR Toxicol. Sci., May 1, 2008; 103(1): 46 - 56. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Kronke, A. Kadl, E. Ikonomu, S. Bluml, A. Furnkranz, I. J. Sarembock, V. N. Bochkov, M. Exner, B. R. Binder, and N. Leitinger Expression of Heme Oxygenase-1 in Human Vascular Cells Is Regulated by Peroxisome Proliferator-Activated Receptors Arterioscler. Thromb. Vasc. Biol., June 1, 2007; 27(6): 1276 - 1282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Nishimura, Y. Dewa, M. Muguruma, Y. Kuroiwa, H. Yasuno, T. Shima, M. Jin, M. Takahashi, T. Umemura, and K. Mitsumori Effect of Fenofibrate on Oxidative DNA Damage and on Gene Expression Related to Cell Proliferation and Apoptosis in Rats Toxicol. Sci., May 1, 2007; 97(1): 44 - 54. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Peraza, A. D. Burdick, H. E. Marin, F. J. Gonzalez, and J. M. Peters The Toxicology of Ligands for Peroxisome Proliferator-Activated Receptors (PPAR) Toxicol. Sci., April 1, 2006; 90(2): 269 - 295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Voss, J. Liu, S. P. Anderson, C. Dunn, J. D. Miller, J. R. Owen, R. T. Riley, C. W. Bacon, and J. C. Corton Toxic Effects of Fumonisin in Mouse Liver Are Independent of the Peroxisome Proliferator-Activated Receptor {alpha} Toxicol. Sci., January 1, 2006; 89(1): 108 - 119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Corton and H. M. Brown-Borg Peroxisome Proliferator-Activated Receptor {gamma} Coactivator 1 in Caloric Restriction and Other Models of Longevity J. Gerontol. A Biol. Sci. Med. Sci., December 1, 2005; 60(12): 1494 - 1509. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
R. A. Currie, V. Bombail, J. D. Oliver, D. J. Moore, F. L. Lim, V. Gwilliam, I. Kimber, K. Chipman, J. G. Moggs, and G. Orphanides Gene Ontology Mapping as an Unbiased Method for Identifying Molecular Pathways and Processes Affected by Toxicant Exposure: Application to Acute Effects Caused by the Rodent Non-Genotoxic Carcinogen Diethylhexylphthalate Toxicol. Sci., August 1, 2005; 86(2): 453 - 469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Stauber, H. Brown-Borg, J. Liu, M. P. Waalkes, A. Laughter, R. A. Staben, J. C. Coley, C. Swanson, K. A. Voss, J. J. Kopchick, et al. Constitutive Expression of Peroxisome Proliferator-Activated Receptor {alpha}-Regulated Genes in Dwarf Mice Mol. Pharmacol., March 1, 2005; 67(3): 681 - 694. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |