Journal article
Identification of a Functional Peroxisome Proliferator-Activated Receptor Response Element in the Rat Catalase Promoter
Molecular endocrinology (Baltimore, Md.), Vol.16(12), pp.2793-2801
12/01/2002
DOI: 10.1210/me.2002-0020
PMID: 12456800
Abstract
Abstract Peroxisomal proliferator-activated receptor (PPAR)γ has been shown to decrease the inflammatory response via transrepression of proinflammatory transcription factors. However, the identity of PPARγ responsive genes that decrease the inflammatory response has remained elusive. Because generation of the reactive oxygen species hydrogen peroxide (H2O2) plays a role in the inflammatory process and activation of proinflammatory transcription factors, we wanted to determine whether the antioxidant enzyme catalase might be a PPARγ target gene. We identified a putative PPAR response element (PPRE) containing the canonical direct repeat 1 motif, AGGTGA-A-AGTTGA, in the rat catalase promoter. In vitro translated PPARγ and retinoic X receptor-α proteins were able to bind to the catalase PPRE. Promoter deletion analysis revealed that the PPRE was functional, and a heterologous promoter construct containing a multimerized catalase PPRE demonstrated that the PPRE was necessary and sufficient for PPARγ-mediated activation. Treatment of microvascular endothelial cells with PPARγ ligands led to increases in catalase mRNA and activity. These results demonstrate that PPARγ can alter catalase expression; this occurs via a PPRE in the rat catalase promoter. Thus, in addition to transrepression of proinflammatory transcription factors, PPARγ may also be modulating catalase expression, and hence down-regulating the inflammatory response via scavenging of reactive oxygen species.
Details
- Title: Subtitle
- Identification of a Functional Peroxisome Proliferator-Activated Receptor Response Element in the Rat Catalase Promoter
- Creators
- Geoffrey D Girnun - Free Radical and Radiation Biology Program (G.D.G., F.E.D., M.E.C.R.), Iowa City, Iowa 52242Frederick E Domann - Free Radical and Radiation Biology Program (G.D.G., F.E.D., M.E.C.R.), Iowa City, Iowa 52242Steven A Moore - Department of Radiation Oncology and Department of Pathology (S.A.M.), University of Iowa, Iowa City, Iowa 52242Mike E. C Robbins - Free Radical and Radiation Biology Program (G.D.G., F.E.D., M.E.C.R.), Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- Molecular endocrinology (Baltimore, Md.), Vol.16(12), pp.2793-2801
- DOI
- 10.1210/me.2002-0020
- PMID
- 12456800
- ISSN
- 0888-8809
- eISSN
- 1944-9917
- Language
- English
- Date published
- 12/01/2002
- Academic Unit
- Pathology; Surgery; Radiation Oncology
- Record Identifier
- 9984047737502771
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