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Molecular Endocrinology, doi:10.1210/me.2002-0020
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Molecular Endocrinology 16 (12): 2793-2801
Copyright © 2002 by The Endocrine Society

Identification of a Functional Peroxisome Proliferator-Activated Receptor Response Element in the Rat Catalase Promoter

Geoffrey D. Girnun1, Frederick E. Domann, Steven A. Moore and Mike E. C. Robbins

Free Radical and Radiation Biology Program (G.D.G., F.E.D., M.E.C.R.), Department of Radiation Oncology and Department of Pathology (S.A.M.), University of Iowa, Iowa City, Iowa 52242

Address all correspondence and requests for reprints to: Mike E. C. Robbins, Ph.D., Department of Radiation Oncology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157. E-mail: mrobbins{at}wfubmc.edu.

Peroxisomal proliferator-activated receptor (PPAR){gamma} has been shown to decrease the inflammatory response via transrepression of proinflammatory transcription factors. However, the identity of PPAR{gamma} 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 PPAR{gamma} 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 PPAR{gamma} and retinoic X receptor-{alpha} 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 PPAR{gamma}-mediated activation. Treatment of microvascular endothelial cells with PPAR{gamma} ligands led to increases in catalase mRNA and activity. These results demonstrate that PPAR{gamma} can alter catalase expression; this occurs via a PPRE in the rat catalase promoter. Thus, in addition to transrepression of proinflammatory transcription factors, PPAR{gamma} may also be modulating catalase expression, and hence down-regulating the inflammatory response via scavenging of reactive oxygen species.

NURSA Molecule Pages Link:

Nuclear Receptors:   PPARγ  |  RXRα
Ligands:   LGD 100268  |  Rosiglitazone



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