Identification of a functional peroxisome proliferator-activated receptor response element in the rat catalase promoter.
Peroxisomal proliferator-activated receptor (PPAR)gamma has been shown to decrease the inflammatory response via transrepression of proinflammatory transcription factors. However, the identity of PPARgamma responsive genes that decrease the inflammatory response has remained elusive. Because generation of the reactive oxygen species hydrogen peroxide (H(2)O(2)) 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 PPARgamma 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 PPARgamma 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 PPARgamma-mediated activation. Treatment of microvascular endothelial cells with PPARgamma ligands led to increases in catalase mRNA and activity. These results demonstrate that PPARgamma can alter catalase expression; this occurs via a PPRE in the rat catalase promoter. Thus, in addition to transrepression of proinflammatory transcription factors, PPARgamma may also be modulating catalase expression, and hence down-regulating the inflammatory response via scavenging of reactive oxygen species.
Girnun
Geoffrey D
GD
Free Radical and Radiation Biology Program, University of Iowa, Iowa City, IA 52242, USA.
Domann
Frederick E
FE
Moore
Steven A
SA
Robbins
Mike E C
ME
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D001483:Base Sequence; D002374:Catalase / Q000235:genetics* / Q000378:metabolism; D019281:Dimerization; D016166:Free Radical Scavengers; D017353:Gene Deletion; D015870:Gene Expression / Q000187:drug effects; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009930:Organic Chemicals; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D020218:Response Elements / Q000235:genetics*; D047488:Retinoid X Receptors; D000077154:Rosiglitazone; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D014162:Transfection
D000924:Anticholesteremic Agents; D016166:Free Radical Scavengers; C423914:LG 268; D009930:Organic Chemicals; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone; D002374:Catalase