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Publication : Overexpression of antioxidant enzymes in transgenic mice decreases cellular ploidy during liver regeneration.

First Author  Nakatani T Year  1997
Journal  Exp Cell Res Volume  236
Issue  1 Pages  137-46
PubMed ID  9344593 Mgi Jnum  J:43473
Mgi Id  MGI:1097774 Doi  10.1006/excr.1997.3715
Citation  Nakatani T, et al. (1997) Overexpression of antioxidant enzymes in transgenic mice decreases cellular ploidy during liver regeneration. Exp Cell Res 236(1):137-46
abstractText  Reactive oxygen species (ROS) and antioxidant enzymes have been implicated in control mechanisms of cellular growth and proliferation. We investigated the influence of levels of endogenous antioxidant enzymes on liver regeneration in transgenic mice overexpressing human Cu,Zn-superoxide dismutase (SOD) and intracellular glutathione peroxidase (GP1) as a model system. After a two-thirds partial hepatectomy (PH), no significant difference was observed in rate of liver mass restoration among nontransgenic, SOD, and GP1 mice. In contrast, the level of polyploidization was significantly reduced in transgenic animals after PH, with a concomitant increase in 2N nuclei. The portion of 8N nuclei after 72 h reached 33.1, 15.8, and 22.1%, whereas the portion of 2N nuclei reached 7.5, 13.8, and 12.3% in nontransgenic, SOD, and GP1 mice, respectively. A similar effect was observed in another model of liver proliferation, during normal development around weaning time. Measurements of ROS production during PH indicate that overexpression of SOD leads to the decreased production of O2- and elevation of H2O2. Unexpectably, overexpression of GP in transgenic mice also results in increased production of H2O2 in hepatocytes. Finally, our data demonstrate that levels of endogenous antioxidant enzymes might influence the rate of hepatocyte polyploidization during liver proliferation.
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