Simm Roger, Kvalvaag Audun Sverre, van Deurs Bo, Lindbäck Toril, Sandvig Kirsten
Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Molecular Cell Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Department of Cellular and Molecular Medicine, The Panum Institute, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
Exp Cell Res. 2017 Aug 1;357(1):67-78. doi: 10.1016/j.yexcr.2017.04.025. Epub 2017 Apr 25.
Benzyl alcohol (BnOH) is widely used as a component of foods, cosmetics, household products and medical products. It is generally considered to be safe for human use, however, it has been connected to a number of adverse effects, including hypersensitivity reactions and neonatal deaths. BnOH is a membrane fluidizing agent that can affect membrane protein activity and cellular processes such as ligand binding to cell surface receptors, endocytosis and degradation of lysosomal cargo. In this study, we examined the effects of BnOH on intracellular transport using Shiga toxin (Stx), diphtheria toxin (DT) and ricin. BnOH caused reduced toxicity of all three toxins at BnOH concentrations that cause membrane fluidization. The reduced toxicity of Stx and ricin was mainly due to inhibition of retrograde transport between endosomes and the trans-Golgi network as BnOH had small effects on cell association and endocytosis of ricin and Stx. Strikingly, BnOH also induced a reversible fragmentation of the Golgi apparatus.
苯甲醇（BnOH）被广泛用作食品、化妆品、家用产品和医疗产品的成分。一般认为它对人体使用是安全的，然而，它与一些不良反应有关，包括过敏反应和新生儿死亡。BnOH是一种膜流化剂，可影响膜蛋白活性和细胞过程，如配体与细胞表面受体的结合、内吞作用和溶酶体货物的降解。在本研究中，我们使用志贺毒素（Stx）、白喉毒素（DT）和蓖麻毒素研究了BnOH对细胞内运输的影响。在导致膜流化的BnOH浓度下，BnOH导致所有三种毒素的毒性降低。Stx和蓖麻毒素毒性降低主要是由于内体与反式高尔基体网络之间的逆行运输受到抑制，因为BnOH对蓖麻毒素和Stx的细胞结合和内吞作用影响较小。引人注目的是，BnOH还诱导了高尔基体的可逆碎片化。
