A Bacillus thuringiensis crystal protein with selective cytocidal action to human cells
A Bacillus thuringiensis crystal protein with selective cytocidal action to human cells
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DOI：
10.1074/jbc.m401881200
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发表时间：
2004-05-14
影响因子：
4.8
通讯作者：
Ohba, M
中科院分区：
文献类型：
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作者：
Ito, A;Sasaguri, Y;Ohba, M
众所周知，苏云金芽孢杆菌晶体蛋白对某些昆虫有毒，但对哺乳动物不致病，在农业和森林管理中用作杀虫蛋白。我们在此鉴定了一种晶体蛋白，其是非杀虫性和非溶血性的，但对具有明显不同靶特异性的各种人类细胞具有强的杀细胞活性，例如，G.对HepG2和Jurkat的细胞毒性高，对正常肝细胞（HC）和HeLa的细胞毒性低。在肝脏和结肠癌组织切片中，毒素蛋白优先杀死癌细胞，而其他细胞不受影响。该蛋白的杀细胞作用是非凋亡的，具有易感细胞的肿胀和碎片，尽管当细胞损伤缓慢进行时确实发生凋亡过程。该蛋白的克隆基因的核苷酸序列推导的氨基酸序列与B的杀虫晶体蛋白的序列同源性很小。苏云金杆菌这些观察结果提出了一个新的B族的存在。苏云金杆菌毒素及其在医学领域新应用的可能性。
Bacillus thuringiensis crystal proteins, well known to be toxic to certain insects but not pathogenic to mammals, are used as insecticidal proteins in agriculture and forest management. We here identified a crystal protein that is non-insecticidal and non-hemolytic but has strong cytocidal activity against various human cells with a markedly divergent target specificity, e. g. highly cytotoxic to HepG2 and Jurkat and less cytotoxic to the normal hepatocyte (HC) and HeLa. In slices of liver and colon cancer tissues, the toxin protein preferentially killed the cancer cells, leaving other cells unaffected. The cytocidal effect of the protein is non-apoptotic with swelling and fragmentation of the susceptible cells, although the apoptotic process does occur when the cell damage proceeded slowly. The amino acid sequence deduced from the nucleotide sequence of the cloned gene of the protein has little sequence homology with the insecticidal crystal proteins of B. thuringiensis. These observations raise the presence of a new group of the B. thuringiensis toxin and the possibility of new applications for the protein in the medical field.