期刊
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
卷 1800, 期 12, 页码 1276-1282出版社
ELSEVIER
DOI: 10.1016/j.bbagen.2010.09.006
关键词
Adenia; HeLa cells; Lanceolin; Ribosome-inactivating proteins; Stenodactylin; Volkensin
资金
- University of Bologna
- Cornelia Legacy for Cancer Research
- Roberto Pallotti Legacy for Cancer Research
- Carisbo Foundation, Bologna
Background: The present research studied the interaction of two ribosome-inactivating proteins (RIPs) from Adenia genus with HeLa cells. Namely, lanceolin and stenodactylin were examined in comparison to volkensin, another toxic two-chain RIP from Adenia genus. Methods: The binding, endocytosis, intracellular routing, degradation and exocytosis were investigated by measuring the distribution of radiolabelled RIP and by determining its cytotoxicity. Results: Stenodactylin was the most toxic, resulting in the greater inhibition of protein synthesis and cell death. Lanceolin and stenodactylin bound to cells with comparable affinity and have a similar number of binding sites (10(5)/cell). The uptake of lanceolin and stenodactylin was 13 and 36 times greater, respectively, than that reported for volkensin. The two toxins bound to cell membrane receptors via their lectin B chain, were endocytosed through a clathrin-independent pathway, were internalised in a manner independent from endosomal acidification, and required routing through the Golgi apparatus, as reported for modeccin and volkensin. Stenodactylin showed greater uptake, exocytosis and re-uptake of non-degraded RIP than lanceolin and volkensin, whereas volkensin had the highest residual activity after being released from the cell. Conclusions: The high cytotoxicity of RIPs from the Adenia genus may depend on the following: high affinity binding to the cell and efficient endocytosis, intracellular routing that appears similar to that of other ricin-like toxic RIPs, partial resistance to proteolysis, and, regarding stenodactylin, high accumulation in cell. General significance: The data provide a model that could lead to new strategies for anti-cancer therapy and neuroscience studies. (C) 2010 Elsevier B.V. All rights reserved.
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