Saponins modulate the intracellular trafficking of protein toxins.
Saponins modulate the intracellular trafficking of protein toxins.
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皂苷调节蛋白质毒素的细胞内运输
DOI：
10.1016/j.jconrel.2012.10.002
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
H. Fuchs
中科院分区：
文献类型：
--
作者：
A. Weng;M. Thakur;B. von Mallinckrodt;F. Beceren-Braun;R. Gilabert-Oriol;B. Wiesner;J. Eichhorst;S. Bottger;M.F. Melzig;H. Fuchs
I型核糖体失活蛋白被广泛用作靶向抗肿瘤毒素的毒素部分，如植物皂角皂苷。为了发挥细胞毒性，毒素部分必须释放到肿瘤细胞的细胞质中。然而，将毒素分子转移到细胞质中是一个低效的过程。在这篇报告中，我们证明了某些皂苷，它们也是由皂角草合成的，特异性地介导皂苷从细胞内区室释放到细胞质中，而不影响质膜的完整性。相关的细胞区室被鉴定为晚期内体和溶酶体。进一步的研究表明，内体酸化是皂苷介导的皂苷释放的先决条件。结合分析表明皂苷与皂苷以ph依赖的方式存在关联。采用基于皂苷的靶向抗肿瘤毒素联合特征皂苷在体内的同基因肿瘤模型中证明了皂苷介导效应的适用性。
Type I ribosome inactivating proteins such as saporin from the plant Saponaria officinalis L. are widely used as toxin moieties of targeted anti-tumor toxins. For exerting cytotoxicity the toxin moieties have to be released into the cytosol of tumor cells. However the cytosolic transfer of toxin molecules into the cytosol is mostly an inefficient process. In this report we demonstrate that certain saponins, which are also biosynthesized by Saponaria officinalis L., specifically mediate the release of saporin out of the intracellular compartments into the cytosol without affecting the integrity of the plasma membrane. The relevant cellular compartments were identified as late endosomes and lysosomes. Further studies revealed that endosomal acidification is a prerequisite for the saponin-mediated release of saporin. Binding analysis demonstrated an association of the saponins with saporin in a pH-dependent manner. The applicability of the saponin-mediated effect was demonstrated in vivo in a syngeneic tumor model using a saporin-based targeted anti-tumor toxin in combination with characterized saponins.
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影响因子：
10.8
作者：
Fuchs, Hendrik;Bachran, Christopher;Sutherland, Mark
通讯作者：
Sutherland, Mark
影响因子：
6.4
作者：
Heisler, I;Keller, J;Fuchs, H
通讯作者：
Fuchs, H
肿瘤治疗中皂苷分离的便捷方法。
DOI：
--
发表时间：
2010
期刊：
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
影响因子：
--
作者：
A. Weng;K. Jenett‐Siems;P. Schmieder;D. Bachran;C. Bachran;C. Görick;M. Thakur;H. Fuchs;M. Melzig
通讯作者：
M. Melzig
靶向抗肿瘤毒素的毒素成分决定了皂苷提高其功效
影响因子：
6.6
作者：
A. Weng;M. Thakur;F. Beceren-Braun;D. Bachran;C. Bachran;S.B. Riese;K. Jenett-Siems;R. Gilabert-Oriol;M.F. Melzig;H. Fuchs
通讯作者：
H. Fuchs
人尿激酶原和植物毒素肥皂草素之间嵌合体的内吞作用：一种不寻常的内化机制
DOI：
10.1096/fasebj.14.10.1335
发表时间：
2000
期刊：
The FASEB Journal
影响因子：
--
作者：
R. Ippoliti;E. Lendaro;P. A. Benedetti;M. Torrisi;F. Belleudi;D. Carpani;M. Soria;M. Fabbrini
通讯作者：
M. Fabbrini