Human catalase gene is regulated by peroxisome proliferator activated receptor-gamma through a response element distinct from that of mouse.
Oxidative stress has been implicated as a causal role in atherosclerosis, microvascular complications of diabetes as well as in beta cell failure in type 2 diabetes. PPARgamma agonists not only improve insulin sensitivity but also eliminate oxidative stress. In mouse, catalase, a major antioxidant enzyme, is directly regulated by PPARgamma through two PPARgamma binding elements in its promoter. This study examined the regulatory mechanisms of catalase expression in human. Expression of catalase was significantly upregulated in human primary adipocytes upon treatment with a PPARgamma agonist. However, the mouse PPARgamma response elements are not functionally conserved in human catalase promoter. In luciferase reporter assay containing human catalase promoter, PPARgamma /RXRalpha, in combination of a PPARgamma agonist significantly transactivated 19 kb of promoter and this was mediated via a novel PPARgamma response element (PPRE) at -12 kb from transcription initiation site of human catalase gene. Electrophoretic mobility shift assay showed direct binding of PPARgamma to this PPRE. Together, our results indicate that PPARgamma regulates the expression of catalase gene in human through a PPRE distinct from that of mouse, and could explain, at least in part, the observed inhibitory effects of PPARgamma on oxidative stress in human.
Okuno
Yosuke
Y
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
Matsuda
Morihiro
M
Miyata
Yugo
Y
Fukuhara
Atsunori
A
Komuro
Ryutaro
R
Shimabukuro
Michio
M
Shimomura
Iichiro
I
D017667:Adipocytes / Q000201:enzymology; D000818:Animals; D001665:Binding Sites; D002374:Catalase / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D051379:Mice; D016297:Mutagenesis, Site-Directed; D018384:Oxidative Stress / Q000502:physiology; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D000077205:Pioglitazone; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020218:Response Elements / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D045162:Thiazolidinediones / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D004247:DNA; D002374:Catalase; D000077205:Pioglitazone