Brefeldin A protects ricin-induced cytotoxicity in human cancer KB cell line, but not in its resistant counterpart with altered Golgi structures.
Brefeldin A protects ricin-induced cytotoxicity in human cancer KB cell line, but not in its resistant counterpart with altered Golgi structures.
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Brefeldin A 可以保护人类癌症 KB 细胞系中蓖麻毒素诱导的细胞毒性，但不能保护高尔基体结构改变的耐药细胞系。
DOI：
10.1247/csf.18.241
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发表时间：
1993
影响因子：
1.5
通讯作者：
M. Kuwano
中科院分区：
文献类型：
--
作者：
Tadayoshi Okimoto;T. Seguchi;M. Ono;Y. Nakayama;G. Funatsu;Toshiyuki Fujiwara;Y. Ikehara;M. Kuwano
布雷菲德菌素A（Brefeldin A，BFA）是一种类异戊二烯真菌代谢产物，能显著干扰细胞内蛋白质转运和蛋白质分泌。BFA保护细胞免受植物毒素、蓖麻毒素或假单胞菌毒素的细胞毒性，但不保护白喉毒素的细胞毒性（Yoshida等人，1991.实验Cell Res.，192：389-395）。在这项研究中，我们研究了是否BFA可以差异改变蓖麻毒素的细胞毒性之间的BFA敏感细胞和BFA耐药细胞。作为BFA抗性细胞系，我们使用了源自BFA敏感性人癌KB细胞的抗性细胞系KB/BF 2 -2。BFA处理引起KB细胞典型的高尔基池消失，同时在细胞质中出现扩张的小泡。与此相反，KB/BF 2 -2细胞已经改变了高尔基体的结构，在没有BFA的情况下，脑池发育不良，也有许多小泡，并且BFA处理没有进一步诱导形态学变化。虽然质膜特异性标记蛋白α-adaptin在KB/BF 2 -2中的定位与KB相似，但在不存在BFA的情况下，高尔基体特异性标记如β-cop和γ-adaptin分布在KB/BF 2 -2细胞的细胞质小囊泡以及高尔基体隔室中，并且突变细胞即使暴露于BFA时也没有显示出分布的明显变化。蓖麻毒素抑制KB和KB/BF 2 -2的蛋白质合成到相似的水平，而用0.1 μ g/ml的BFA预处理KB细胞几乎完全逆转蓖麻毒素的抑制作用。相比之下，KB/BF 2 -2细胞预暴露于1.0微克/毫升的BFA仅部分地挽救蓖麻毒素诱导的蛋白质合成抑制。在加入蓖麻毒素前30 min或加入蓖麻毒素0 min时暴露于BFA可挽救蛋白质合成抑制，但在加入蓖麻毒素后30 min加入BFA时没有发生挽救。BFA不能挽救另一种毒素白喉毒素对蛋白质合成的抑制。我们的研究结果表明，BFA抗性突变引起的蓖麻毒素在人体细胞内的胞吞膜交通的具体变化，也白喉毒素的细胞毒性不共享一个共同的途径的胞内运输与蓖麻毒素。
Brefeldin A (BFA), an isoprenoid fungal metabolite, dramatically disrupts intracellular protein transport and protein secretion. BFA protects cells from the cytotoxicity of a plant toxin, ricin or pseudomonas toxin, but not that of diphtheria toxin (Yoshida et al., 1991. Expt. Cell Res., 192: 389-395.). In this study, we examined whether BFA could differentially change the cytotoxicity of ricin between BFA-sensitive cells and BFA-resistant cells. As a BFA-resistant cell line, we used a resistant cell line, KB/BF2-2, derived from BFA-sensitive human cancer KB cells. BFA treatment caused the disappearance of typical Golgi cisternae and the concomitant appearance of dilated vesicles in the cytoplasm in KB cells. By contrast, KB/BF2-2 cells had already altered Golgi structures with poor development of cisternae and also many vesicles in the absence of BFA, and BFA treatment did not further induce the morphological changes. Although a plasma membrane-specific marker protein, alpha-adaptin, was localized similarly in KB/BF2-2 as KB, Golgi specific markers such as beta-cop and gamma-adaptin were distributed in the cytoplasmic small vesicles as well as Golgi compartments in KB/BF2-2 cells in the absence of BFA, and the mutant cells showed no apparent changes in the distribution even when exposed to BFA. Ricin inhibited protein synthesis in KB and KB/BF2-2 to similar levels while pretreatment of KB cells with BFA at 0.1 microgram/ml almost completely reversed the inhibitory effect of ricin. By contrast, the pre-exposure of KB/BF2-2 cells to 1.0 microgram/ml BFA only partially rescued the ricin-induced inhibition of protein synthesis. Exposure to BFA at 30 min before ricin addition or at 0 min with ricin rescued the protein synthesis inhibition, but no rescue occurred when BFA was added 30 min after ricin addition. BFA could not rescue the protein synthesis inhibition by another toxin, diphtheria toxin. Our results suggest that BFA-resistant mutation causes a specific change in the endocytic membrane traffic of ricin in human cells, and also that cytotoxicity of diphtheria toxin does not share a common pathway of the intracellular transport with that of ricin.
影响因子：
3.7
作者：
T. Yoshida;C. Chen;M. Zhang;H. C. Wu
通讯作者：
T. Yoshida;C. Chen;M. Zhang;H. C. Wu
在中国仓鼠卵巢细胞的假定高尔基体缺陷突变体中，蓖麻毒素的细胞毒性增加。
影响因子：
3.7
作者：
Yoshida,T;Chen,CH;Zhang,MS;Wu,HC
通讯作者：
Wu,HC