Transgenic models for the study of lung antioxidant defense: Enhanced manganese-containing superoxide dismutase activity gives partial protection to B6C3 hybrid mice exposed to hyperoxia
Transgenic models for the study of lung antioxidant defense: Enhanced manganese-containing superoxide dismutase activity gives partial protection to B6C3 hybrid mice exposed to hyperoxia
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DOI：
10.1165/ajrcmb.18.4.2959
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发表时间：
1998-04-01
影响因子：
6.4
通讯作者：
Crapo, JD
中科院分区：
文献类型：
--
作者：
Ho, YS;Vincent, R;Crapo, JD
为了研究含锰超氧化物歧化酶（MnSOD）在肺抗氧化防御中的作用，建立了转基因B6 C3杂交小鼠品系，该小鼠携带在人β-肌动蛋白启动子转录控制下的人MnSOD转基因。表达研究表明，人MnSOD转基因在TgHMS 66系中表达并发挥功能。通过免疫细胞化学分析进一步检查转基因产物在肺中的细胞分布。在肺I型上皮细胞、II型上皮细胞、毛细血管内皮细胞和成纤维细胞的线粒体中发现免疫反应性MnSOD增加。此外，增加线粒体标记密度的非转基因，半合子，纯合子转基因同窝仔的II型细胞的幅度是成比例的肺MnSOD活性增加，发现在这些小鼠。当暴露于> 99%的氧气时，相对于对照组，过表达MnSOD的转基因小鼠的存活率没有提高。然而，当暴露在90%的氧气中时，转基因小鼠的存活时间略有增加，但具有统计学意义。我们的研究结果表明，当β-肌动蛋白启动子被用来增加MnSOD的活性，它提供了适度的保护B6 C3小鼠对高氧肺损伤。
To investigate the role of manganese-containing superoxide dismutase (MnSOD) in lung antioxidant defense, lines of transgenic B6C3 hybrid mice carrying human MnSOD transgenes under the transcriptional control of a human beta-actin promoter were established. Expression studies demonstrated that the human MnSOD transgene in line TgHMS66 is expressed and functional. The cellular distribution of the transgene product in the lungs was further examined by immunocytochemical analysis. Increased immunoreactive MnSOD was found in mitochondria of lung type I epithelial cells, type II epithelial cells, capillary endothelial cells, and fibroblasts. Furthermore, the magnitude of increase in mitochondrial labeling density of type II cells of nontransgenic, hemizygous, and homozygous transgenic littermates was proportional to the increased lung activity of MnSOD found in these mice. Transgenic mice over-expressing MnSOD did not have enhanced survival relative to controls when exposed to > 99% oxygen. However, when exposed to 90% oxygen, the transgenic mice had a small but statistically significant increase in survival time. Our results indicate that when the beta-actin promoter is used to increase activity of MnSOD it provides modest protection to B6C3 mice against hyperoxic lung injury.