Maternally transmitted milk containing recombinant human catalase provides protection against oxidation for mouse offspring during lactation

Maternally transmitted milk containing recombinant human catalase provides protection against oxidation for mouse offspring during lactation
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DOI:
10.1016/j.freeradbiomed.2008.07.019
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发表时间:
2008-10-15
影响因子:
7.4
通讯作者:
Li, Ning
Li, Ning
中科院分区:
医学1区
文献类型:
--
作者:
He, Zuyong;Yu, Shengli;Li, Ning

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过氧化氢酶通过降解过剩的过氧化氢,在保护生物体免受活性氧(ROS)引起的氧化损伤中发挥重要作用。外源过氧化氢酶的加入可以减轻活性氧引起的损伤。因此,通过基因工程生产人过氧化氢酶将满足对这种酶日益增长的治疗需求。在本研究中,我们成功地在小鼠乳腺中表达了重组基因,并将具有生物活性的人过氧化氢酶分泌到转基因小鼠的乳汁中。过氧化氢酶基因中的过氧化物酶体靶向序列(PTS)对重组蛋白的分泌没有明显的负面影响。转基因牛奶的摄入量被认为是减少脂质过氧化,增加总超氧化物歧化酶(T-SOD)的活性在大脑中,并提高总抗氧化能力(T-AOC)的大脑,肝脏和血清。据我们所知,这是在转基因动物的乳汁中有效生产生物活性人过氧化氢酶的第一个例子。我们的研究表明,在转基因农场动物中大规模生产将产生足够的人类过氧化氢酶用于生物医学研究和临床治疗。(C)2008年由Elsevier Inc.出版
Catalase plays an important role in Protecting organisms against oxidative damage caused by reactive oxygen species (ROS) by degrading surplus hydrogen peroxide. Addition of exogenous catalase can alleviate injuries caused by ROS. Thus, production of human catalase through genetic engineering will meet the increasing therapeutic demand for this enzyme. In this study, we successfully expressed the recombinant gene in mouse mammary gland, and biologically active human catalase was secreted into the milk of the transgenic mice. The peroxisomal targeting sequence (PTS) within the catalase gene had no significant negative effect on the secretion of the recombinant protein. Intake of the transgenic milk by the pups was found to decrease lipid peroxidation, increase the total superoxide dismutase (T-SOD) activity in the brain, and enhance the total antioxidative capacity (T-AOC) of brain, liver, and serum. To our knowledge, this is the first example of efficient production of biologically active human catalase in the milk of transgenic animals. Our study suggests that scaled-up production in transgenic farm animals would yield sufficient human catalase for biomedical research and clinical therapies. (C) 2008 Published by Elsevier Inc.