Enhanced plasminogen activator inhibitor-1 expression in transgenic mice with hepatocyte-specific overexpression of superoxide dismutase or glutathione peroxidase

Antioxidants & Redox Signaling
Kai FrankeThomas Kietzmann

Abstract

In this study, we developed a double-transgenic mouse model allowing hepatocyte-specific and regulated expression of the redox-modifying enzymes copper/zinc superoxide dismutase (SOD) and glutathione peroxidase (GPX) by using a tetracycline-regulatable gene expression system. Within this system, the SOD and GPX level can be regulated deliberately by addition or removal of doxycycline hydrochloride to the drinking water. As reactive oxygen species (ROS) have been implicated in a number of pathological conditions, such as atherosclerosis, thrombosis, or liver fibrosis, processes that are also frequently associated with enhanced levels of plasminogen activator inhibitor-1 (PAI-1), it was the aim of the present study to investigate the influence of SOD and GPX overexpression on the regulation of PAI-1. PAI-1 mRNA and protein levels in tetracycline transactivator-dependent SOD-overexpressing double-transgenic mice reached values 2.5- to threefold above the normal mRNA level. By applying doxycycline, a deinduction of the PAI-1 levels was observed. By using the same protocol, PAI-1 mRNA and protein levels were enhanced in GPX double-transgenic mice, and again this response was blunted by the addition of doxycycline. These studies prov...Continue Reading

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Citations

Aug 31, 2012·The Journal of Biological Chemistry·Gunda MillonigSebastian Mueller
Jul 10, 2004·Antioxidants & Redox Signaling·Agnes Görlach
Aug 24, 2005·Antioxidants & Redox Signaling·Agnes Görlach
Nov 26, 2013·Biochimica Et Biophysica Acta·Kimberly J RiehleJean S Campbell
Mar 3, 2004·Free Radical Biology & Medicine·Vuokko L Kinnula, James D Crapo
Mar 15, 2020·International Journal of Molecular Sciences·Clemens GutmannAlberto Smith
May 22, 2021·International Immunopharmacology·Salvatore ChirumboloSergio Pandolfi

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