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利用表达人金属硫蛋白-I融合蛋白的重组乳酸乳球菌预防胃肠道铅中毒。

Prevention of gastrointestinal lead poisoning using recombinant Lactococcus lactis expressing human metallothionein-I fusion protein.

作者信息

Xiao Xue, Zhang Changbin, Liu Dajun, Bai Weibin, Zhang Qihao, Xiang Qi, Huang Yadong, Su Zhijian

机构信息

Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, P.R. China.

Department of Clinical Molecular Diagnosis, Guangdong Women and Children Hospital, Guangzhou 510010, P.R. China.

出版信息

Sci Rep. 2016 Apr 5;6:23716. doi: 10.1038/srep23716.

DOI:10.1038/srep23716
PMID:27045906
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4820694/
Abstract

Low-level lead poisoning is an insidious disease that affects millions of children worldwide, leading to biochemical and neurological dysfunctions. Blocking lead uptake via the gastrointestinal tract is an important prevention strategy. With this in mind, we constructed the recombinant Lactococcus lactis strain pGSMT/MG1363, which constitutively expressed the fusion protein glutathione S-transferase (GST)-small molecule ubiquitin-like modifier protein (SUMO)-metallothionein-I (GST-SUMO-MT). The thermodynamic data indicated that the average number of lead bound to a GST-SUMO-MT molecule was 3.655 and this binding reaction was a spontaneous, exothermic and entropy-increasing process. The total lead-binding capacity of pGSMT/MG1363 was 4.11 ± 0.15 mg/g dry mass. Oral administration of pGSMT/MG1363 (1 × 10(10) Colony-Forming Units) to pubertal male rats that were also treated with 5 mg/kg of lead acetate daily significantly inhibited the increase of blood lead levels, the impairment of hepatic function and the decrease of testosterone concentration in the serum, which were all impaired in rats treated by lead acetate alone. Moreover, the administration of pGSMT/MG1363 for 6 weeks did not affect the serum concentration of calcium, magnesium, potassium or sodium ions. This study provides a convenient and economical biomaterial for preventing lead poisoning via the digestive tract.

摘要

低水平铅中毒是一种隐匿性疾病,影响着全球数百万儿童,会导致生物化学和神经功能障碍。通过胃肠道阻断铅的吸收是一项重要的预防策略。基于此,我们构建了重组乳酸乳球菌菌株pGSMT/MG1363,其组成型表达融合蛋白谷胱甘肽S-转移酶(GST)-小分子泛素样修饰蛋白(SUMO)-金属硫蛋白-I(GST-SUMO-MT)。热力学数据表明,与一个GST-SUMO-MT分子结合的铅的平均数量为3.655,且这种结合反应是一个自发的、放热的和熵增加的过程。pGSMT/MG1363的总铅结合能力为4.11±0.15mg/g干重。对每天还接受5mg/kg醋酸铅处理的青春期雄性大鼠口服pGSMT/MG1363(1×10¹⁰菌落形成单位),显著抑制了血铅水平的升高、肝功能的损害以及血清中睾酮浓度的降低,而单独用醋酸铅处理的大鼠这些指标均受到了损害。此外,给予pGSMT/MG1363 6周对血清中钙、镁、钾或钠离子的浓度没有影响。本研究提供了一种方便且经济的生物材料,用于通过消化道预防铅中毒。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b266/4820694/6a18c3f2d33e/srep23716-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b266/4820694/5a5e88322810/srep23716-f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b266/4820694/bcff6143a0aa/srep23716-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b266/4820694/7768052d509d/srep23716-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b266/4820694/6a18c3f2d33e/srep23716-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b266/4820694/5a5e88322810/srep23716-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b266/4820694/55dadfee5eb9/srep23716-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b266/4820694/5f6af1227557/srep23716-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b266/4820694/7e98a053a4b9/srep23716-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b266/4820694/be8368d1340e/srep23716-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b266/4820694/bcff6143a0aa/srep23716-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b266/4820694/7768052d509d/srep23716-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b266/4820694/6a18c3f2d33e/srep23716-f8.jpg

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