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