Abstract

The purpose is to pursue investigations to delineate the acute and long-term effects of hypolipidemic hepatic peroxisome proliferators, in an attempt to understand the biologic significance of peroxisomes in general and peroxisome proliferation in particular. We will expend considerable effort toward evaluating biologic events associated with hepatic peroxisome proliferation. These studies will include: screening of selected chemicals of unusual structure with potent hypolipidemic activity for induction of peroxisome proliferation and peroxisome-associated enzymes in hepatic and extrahepatic cells, characterization of peroxisome membrane by freeze-fracturing, purification and subcellular localization of 80,000 MW protein induced in liver by hepatic perosisome proliferators, and induction and degradation of peroxisomes and peroxisome-associated enzymes in vitro in isolated liver cells. In addition, the proposed research will also strive to establish, as well as elucidate, the role, if any of persistent peroxisome proliferation and hepatomegaly induced by the hepatic peroxisome proliferators in the initiation and promotion of hepatocellular carcinomas in rats. The information obtained from these studies should further our knowledge of peroxisomes as well as allow us to recognize the implications of the multiplicity of biologic effects of peroxisome proliferators.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM023750-10
Application #
3271859
Study Section
Pathology B Study Section (PTHB)
Project Start
1976-06-30
Project End
1987-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
10
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Northwestern University at Chicago
Department
Type
School of Medicine & Dentistry
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611

  Publications

Huang, Jiansheng; Jia, Yuzhi; Fu, Tao et al. (2012) Sustained activation of PPAR? by endogenous ligands increases hepatic fatty acid oxidation and prevents obesity in ob/ob mice. FASEB J 26:628-38
Vluggens, Aurore; Reddy, Janardan K (2012) Nuclear receptors and transcription factors in the development of fatty liver disease. Curr Drug Metab 13:1422-35
Bai, Liang; Jia, Yuzhi; Viswakarma, Navin et al. (2011) Transcription coactivator mediator subunit MED1 is required for the development of fatty liver in the mouse. Hepatology 53:1164-74
Huang, Jiansheng; Viswakarma, Navin; Yu, Songtao et al. (2011) Progressive endoplasmic reticulum stress contributes to hepatocarcinogenesis in fatty acyl-CoA oxidase 1-deficient mice. Am J Pathol 179:703-13
Hall, Angela M; Brunt, Elizabeth M; Chen, Zhouji et al. (2010) Dynamic and differential regulation of proteins that coat lipid droplets in fatty liver dystrophic mice. J Lipid Res 51:554-63
Matsumoto, Kojiro; Huang, Jiansheng; Viswakarma, Navin et al. (2010) Transcription coactivator PBP/MED1-deficient hepatocytes are not susceptible to diethylnitrosamine-induced hepatocarcinogenesis in the mouse. Carcinogenesis 31:318-25
Stumpf, Melanie; Yue, Xiaojing; Schmitz, Sandra et al. (2010) Specific erythroid-lineage defect in mice conditionally deficient for Mediator subunit Med1. Proc Natl Acad Sci U S A 107:21541-6
Vluggens, Aurore; Andreoletti, Pierre; Viswakarma, Navin et al. (2010) Reversal of mouse Acyl-CoA oxidase 1 (ACOX1) null phenotype by human ACOX1b isoform [corrected]. Lab Invest 90:696-708
Jia, Yuzhi; Viswakarma, Navin; Fu, Tao et al. (2009) Conditional ablation of mediator subunit MED1 (MED1/PPARBP) gene in mouse liver attenuates glucocorticoid receptor agonist dexamethasone-induced hepatic steatosis. Gene Expr 14:291-306
Li, Hui; Gade, Padmaja; Nallar, Shreeram C et al. (2008) The Med1 subunit of transcriptional mediator plays a central role in regulating CCAAT/enhancer-binding protein-beta-driven transcription in response to interferon-gamma. J Biol Chem 283:13077-86

Showing the most recent 10 out of 104 publications