Cheng W H, Ho Y S, Ross D A, Han Y, Combs G F, Lei X G
Department of Animal Science, Cornell University, Ithaca, NY 14853, USA.
J Nutr. 1997 May;127(5):675-80. doi: 10.1093/jn/127.5.675.
Selenium-dependent cellular glutathione peroxidase (GPX1) overexpressing [GPX1(+)] mice were derived by microinjecting a 5.3-kb cloned entire mouse GPX1 genomic DNA into fertilized eggs. The objective of this study was to determine the effect of GPX1 overexpression and dietary selenium on the expression of selenoperoxidases and the status of lipid peroxidation of these transgenic animals. An experiment with a 2 x 2 factorial arrangement of treatments with 15 GPX1(+) and 15 control mice (2 mo old) was conducted for 8 wk. Ten mice of each group (half males and females) were fed a Se-deficient, Torula yeast basal diet (0.02 mg Se/kg, no supplemental vitamin E) and five mice (three males and two females) were fed the basal diet supplemented with 0.51 mg Se/kg as Na2SeO3. The GPX1(+) mice had greater GPX1 activities (one- to sixfold, P < 0.0001) than the control mice at both levels of dietary selenium in all tissues except for liver, in which such difference (100%, P < 0.05) was observed only in Se-deficient mice. The GPX1 mRNA level in kidney and in lung of the Se-deficient GPX1(+) mice was 81% and 7.5-fold greater (P < 0.003) than the respective control level. Overexpression of GPX1 did not alter phospholipid hydroperoxide glutathione peroxidase (GPX4) activities and mRNA levels or glutathione S-transferase (GST) activities in most of the tissues, plasma glutathione peroxidase (GPX3) activity or plasma Se concentrations. No differences in lipid peroxidation in kidney, lung or intestine were observed between the Se-deficient GPX1(+) and control mice. In conclusion, the overexpression of the GPX1 gene in these mice was tissue specific and did not affect the expression of GPX3, GPX4 or GST and plasma Se levels; dietary Se appeared to affect the GPX1 overexpression at its mRNA level.
通过将5.3kb克隆的完整小鼠GPX1基因组DNA显微注射到受精卵中，获得了硒依赖性细胞谷胱甘肽过氧化物酶（GPX1）过表达[GPX1(+)]小鼠。本研究的目的是确定GPX1过表达和膳食硒对这些转基因动物硒过氧化物酶表达和脂质过氧化状态的影响。对15只GPX1(+)小鼠和15只对照小鼠（2月龄）进行了为期8周的2×2析因实验。每组10只小鼠（雌雄各半）喂食缺硒的圆酵母基础日粮（0.02mg硒/kg，无补充维生素E），5只小鼠（3只雄性和2只雌性）喂食补充了0.51mg硒/kg亚硒酸钠的基础日粮。在除肝脏外的所有组织中，在两种膳食硒水平下，GPX1(+)小鼠的GPX1活性均高于对照小鼠（1至6倍，P<0.0001），而在肝脏中，这种差异（100%，P<0.05）仅在缺硒小鼠中观察到。缺硒的GPX1(+)小鼠肾脏和肺中的GPX1 mRNA水平分别比各自对照水平高81%和7.5倍（P<0.003）。GPX1的过表达并未改变大多数组织中的磷脂氢过氧化物谷胱甘肽过氧化物酶（GPX4）活性和mRNA水平、谷胱甘肽S-转移酶（GST）活性、血浆谷胱甘肽过氧化物酶（GPX3）活性或血浆硒浓度。缺硒的GPX1(+)小鼠与对照小鼠在肾脏、肺或肠道的脂质过氧化方面未观察到差异。总之，这些小鼠中GPX1基因的过表达具有组织特异性且不影响GPX3、GPX4或GST的表达以及血浆硒水平；膳食硒似乎在mRNA水平上影响GPX1的过表达。
