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Endocrine Journal
Vol. 57 (2010) No. 4 P 303-309

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http://doi.org/10.1507/endocrj.K09E-113

ORIGINALS

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. PPARγ agonists not only improve insulin sensitivity but also eliminate oxidative stress. In mouse, catalase, a major antioxidant enzyme, is directly regulated by PPARγ through two PPARγ 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 PPARγ agonist. However, the mouse PPARγ response elements are not functionally conserved in human catalase promoter. In luciferase reporter assay containing human catalase promoter, PPARγ /RXRα, in combination of a PPARγ agonist significantly transactivated 19 kb of promoter and this was mediated via a novel PPARγ response element (PPRE) at -12 kb from transcription initiation site of human catalase gene. Electrophoretic mobility shift assay showed direct binding of PPARγ to this PPRE. Together, our results indicate that PPARγ 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 PPARγ on oxidative stress in human.

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