Peroxisomal proliferator-activated receptor-alpha-dependent inhibition of endothelial cell proliferation and tumorigenesis.

Peroxisomal proliferator-activated receptor-alpha-dependent inhibition of endothelial cell proliferation and tumorigenesis. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Peroxisomal proliferator-activated receptor-alpha-dependent inhibition of endothelial cell proliferation and tumorigenesis. Abstract Text:

Ambra Pozzi,Maria Raquel Ibanez,Arnaldo E Gatica,Shilin Yang,Shouzuo Wei,Shaojun Mei,John R Falck,Jorge H Capdevila,

The peroxisomal proliferator-activated nuclear receptor-alpha (PPARalpha), the target for most hypolipidemic drugs in current clinical use, regulates the transcription of genes involved in lipid metabolism and transport, and energy homeostasis. More recently, PPARalpha and its ligands have been implicated in inflammatory responses and the regulation of cell proliferation. PPARalpha also regulates the expression of Cyp4a fatty acid omega-hydroxylases and Cyp2c arachidonic acid epoxygenase genes. To study the role of the PPARalpha receptor and of its Cyp2c epoxygenase gene target in tumorigenesis, we treated mice injected with tumor cells with Wy-14,643, a PPARalpha-selective ligand. Compared with untreated controls, Wy-14643-treated animals showed marked reductions in tumor growth and vascularization, which were accompanied by decreases in the plasma levels of pro-angiogenic epoxygenase metabolites (EETs), hepatic EET biosynthesis, and Cyp2c epoxygenase expression. All these Wy-14643-induced responses were absent in PPARalpha(-/-) mice and are thus PPARalpha-mediated. Primary cultures of mouse lung endothelial cells treated with Wy-14643 showed reductions in cell proliferation and in the formation of capillary-like structures. These effects were absent in cells obtained from PPRAalpha(-/-) mice and reversed by the addition of EETs. These results identify important anti-angiogenic and anti-tumorigenic roles for PPARalpha, characterize the contribution of its Cyp2c epoxygenases gene target to these responses, and suggest potential anti-cancer roles for this nuclear receptor and its ligands.

Peroxisomal proliferator-activated receptor-alpha-dependent inhibition of endothelial cell proliferation and tumorigenesis. Publishing Authors By Initials

A Pozzi,MR Ibanez,AE Gatica,S Yang,S Wei,S Mei,JR Falck,JH Capdevila,

For similar heterocyclic compounds: heterocyclic compounds, 1-ring: pyrimidines research abstracts see: heterocyclic compounds: heterocyclic compounds, 1-ring: pyrimidines research

PUBMED ID PMID:

MEDLINE DATE:

Peroxisomal proliferator-activated receptor-alpha-dependent inhibition of endothelial cell proliferation and tumorigenesis. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 17685-95

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 3

MONTH: 04

YEAR: 2007

Peroxisomal proliferator-activated receptor-alpha-dependent inhibition of endothelial cell proliferation and tumorigenesis. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

Peroxisomal proliferator-activated receptor-alpha-dependent inhibition of endothelial cell proliferation and tumorigenesis. Keywords Mesh Terms:

KEYWORDS: Pyrimidines

MESH TERMS: metabolism

Chemical & Substance for Abstract: Peroxisomal proliferator-activated receptor-alpha-dependent inhibition of endothelial cell proliferation and tumorigenesis. Information

Substance Name: Cytochrome P-450 Enzyme System

Registry Number: 9035-51-2

Grant and Affiliation Information for Peroxisomal proliferator-activated receptor-alpha-dependent inhibition of endothelial cell proliferation and tumorigenesis.

AFFILIATION: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: R01-GM37922

ACRONYM: GM

MEDLINETA: J Biol Chem

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Peroxisomal proliferator-activated receptor-alpha-dependent inhibition of endothelial cell proliferation and tumorigenesis Related Publications

• Abnormalities of the Bereitschaftspotential and MRI pallidal signal in non-encephalopathic cirrhotic patients.
• Avoiding propofol injection pain in children: a prospective, randomized, double-blinded, placebo-controlled study.
• Beck Depression Inventory factors related to demyelinating lesions of the left arcuate fasciculus region.
• Comparative insight into the Zn(II)-, Cd(II)- and Cu(I)-binding features of the protozoan Tetrahymena pyriformis MT1 metallothionein.
• Images in clinical medicine. Spontaneous otogenic pneumocephalus.
• Localized amyloidosis of the breast associated with invasive lobular carcinoma.
• PPARalpha Ligands as Antitumorigenic and Antiangiogenic Agents.
• Peroxisomal proliferator-activated receptor-alpha-dependent inhibition of endothelial cell proliferation and tumorigenesis.
• Preparation of N-tBoc L-glutathione dimethyl and di-tert-butyl esters: versatile synthetic building blocks.
• Regulation of ion transport and blood pressure by cytochrome p450 monooxygenases.
• Spatial sampling for night levels estimation in urban environments.
• Structural determinants of active site binding affinity and metabolism by cytochrome P450 BM-3.
• [Freeman-Sheldon's syndrome. Report of five cases]
• [Statistical study of 141 cases of strophulus examined in the dermatology service of the Catedra Universitaria de Barcelona.]