转基因小鼠中抗氧化酶的过表达会降低肝脏再生过程中的细胞倍性。

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

作者信息

Nakatani T, Inouye M, Mirochnitchenko O

机构信息

Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine, Piscataway, New Jersey 08854, USA.

出版信息

Exp Cell Res. 1997 Oct 10;236(1):137-46. doi: 10.1006/excr.1997.3715.

DOI:10.1006/excr.1997.3715

PMID:9344593

Abstract

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.

摘要

活性氧（ROS）和抗氧化酶参与了细胞生长和增殖的调控机制。我们以过表达人铜锌超氧化物歧化酶（SOD）和细胞内谷胱甘肽过氧化物酶（GP1）的转基因小鼠为模型系统，研究了内源性抗氧化酶水平对肝脏再生的影响。在进行三分之二部分肝切除（PH）后，非转基因、SOD和GP1小鼠在肝脏质量恢复速率上未观察到显著差异。相反，PH后转基因动物的多倍体化水平显著降低，同时二倍体细胞核数量增加。72小时后，8倍体细胞核的比例在非转基因、SOD和GP1小鼠中分别达到33.1%、15.8%和22.1%，而二倍体细胞核的比例分别达到7.5%、13.8%和12.3%。在另一个肝脏增殖模型中，即在断奶期正常发育过程中也观察到了类似的效应。PH期间ROS产生的测量结果表明，SOD的过表达导致超氧阴离子（O2-）产生减少和过氧化氢（H2O2）水平升高。出乎意料的是，转基因小鼠中GP的过表达也导致肝细胞中H2O2产生增加。最后，我们的数据表明，内源性抗氧化酶水平可能会影响肝脏增殖过程中肝细胞多倍体化的速率。