Nambiar M P, Wu H C
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799, USA.
Exp Cell Res. 1995 Aug;219(2):671-8. doi: 10.1006/excr.1995.1278.
Ilimaquinone (IQ), a metabolite from sea sponges, has been shown to cause the breakdown of Golgi membranes into small vesicular structure and to inhibit protein transport without eliciting the retrograde transport of the Golgi enzymes to the endoplasmic reticulum [P. A. Takizawa, J. K. Yucel, B. Viet, D. J. Faulkner, T. Deerinck, G. Soto, M. Ellismann, and V. Malhotra, Cell (1993) 73, 1079-1090]. We have found that incubation of Vero cells with IQ inhibited the cytotoxicity of ricin in a dose-dependent manner. The inhibition was reversed upon the removal of IQ. Neither binding and internalization of 125I-ricin nor the translocation of ricin to the cytosol was affected by IQ. However, IQ significantly inhibited the recycling and degradation of internalized 125I-ricin. Preincubation with IQ also prevented the enhancement of ricin cytotoxicity by NH4Cl or nigericin. The inhibition of ricin cytotoxicity by IQ was observed in the presence of cycloheximide, indicating that de novo protein synthesis is not required for IQ-mediated protection of Vero cells from ricin cytotoxicity. In contrast to perinuclear distribution of TRITC-labeled ricin in Vero cells, TRITC-ricin appeared in numerous small vesicles dispersed throughout the cytoplasm in IQ-treated Vero cells. Double labeling with C6-NBD-ceramide and TRITC-labeled ricin showed that these ricin-containing vesicles were distinct from the IQ-induced breakdown product of the Golgi membranes. Like brefeldin A (BFA), IQ inhibited the cytotoxicities of abrin, modeccin, Pseudomonas toxin, and Shiga-like toxin in Vero cells. Unlike BFA, IQ also inhibited the cytotoxicity of diphtheria toxin (DT). Inhibition of DT cytotoxicity was the consequence of a decreased specific binding of the toxin in the IQ-treated cells.
伊利马醌（IQ）是一种来自海绵的代谢产物，已被证明可导致高尔基体膜分解为小泡状结构，并抑制蛋白质运输，而不会引发高尔基体酶向内质网的逆行运输[P. A. 泷泽、J. K. 尤塞尔、B. 维特、D. J. 福克纳、T. 迪林克、G. 索托、M. 埃利斯曼和V. 马尔霍特拉，《细胞》（1993年）73卷，第1079 - 1090页]。我们发现，用IQ处理Vero细胞可剂量依赖性地抑制蓖麻毒素的细胞毒性。去除IQ后，这种抑制作用可逆转。IQ对125I - 蓖麻毒素的结合和内化以及蓖麻毒素向细胞质的转运均无影响。然而，IQ显著抑制内化的125I - 蓖麻毒素的再循环和降解。用IQ预孵育还可防止NH4Cl或尼日利亚菌素增强蓖麻毒素的细胞毒性。在存在环己酰亚胺的情况下观察到IQ对蓖麻毒素细胞毒性的抑制作用，这表明IQ介导的Vero细胞免受蓖麻毒素细胞毒性的保护作用不需要从头合成蛋白质。与TRITC标记的蓖麻毒素在Vero细胞中呈核周分布不同，在IQ处理的Vero细胞中，TRITC - 蓖麻毒素出现在分散于整个细胞质中的许多小泡中。用C6 - NBD - 神经酰胺和TRITC标记的蓖麻毒素进行双重标记表明，这些含有蓖麻毒素的小泡与IQ诱导的高尔基体膜分解产物不同。与布雷菲德菌素A（BFA）一样，IQ抑制Vero细胞中相思子毒素、莫德菌素、铜绿假单胞菌毒素和志贺样毒素的细胞毒性。与BFA不同的是，IQ还抑制白喉毒素（DT）的细胞毒性。DT细胞毒性的抑制是由于IQ处理的细胞中毒素特异性结合减少所致。
