Translocation of botulinum neurotoxin serotype A and associated proteins across the intestinal epithelia
| العنوان: | Translocation of botulinum neurotoxin serotype |
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| المؤلفون: | Luisa W. Cheng, Larry H. Stanker, Rongsheng Jin, Kwangkook Lee, Tina I. Lam |
| المصدر: | Cellular microbiology, vol 17, iss 8 Cellular Microbiology Lam, TI; Stanker, LH; Lee, K; Jin, R; & Cheng, LW. (2015). Translocation of botulinum neurotoxin serotype A and associated proteins across the intestinal epithelia. Cellular Microbiology. doi: 10.1111/cmi.12424. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/32h2p6bzTest |
| بيانات النشر: | Hindawi Limited, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Time Factors, Botulinum Toxins, Macromolecular Substances, media_common.quotation_subject, Immunology, Chromosomal translocation, Biology, medicine.disease_cause, Models, Biological, Microbiology, Type A, law.invention, Mice, Intestinal mucosa, Models, law, Virology, medicine, Animals, Humans, Botulinum Toxins, Type A, Intestinal Mucosa, Internalization, media_common, Gastrointestinal tract, Toxin, Epithelial Cells, Original Articles, Biological, 3. Good health, Transport protein, Protein Transport, Medical Microbiology, Caco-2, Recombinant DNA, Caco-2 Cells, Carrier Proteins |
| الوصف: | © 2015 The Authors. Cellular Microbiology published by John Wiley & Sons Ltd. Botulinum neurotoxins (BoNTs) are some of the most poisonous natural toxins. Botulinum neurotoxins associate with neurotoxin-associated proteins (NAPs) forming large complexes that are protected from the harsh environment of the gastrointestinal tract. However, it is still unclear how BoNT complexes as large as 900kDa traverse the epithelial barrier and what role NAPs play in toxin translocation. In this study, we examined the transit of BoNT serotype A (BoNT/A) holotoxin, complex and recombinantly purified NAP complex through cultured and polarized Caco-2 cells and, for the first time, in the small mouse intestine. Botulinum neurotoxin serotype A and NAPs in the toxin complex were detectable inside intestinal cells beginning at 2h post intoxication. Appearance of the BoNT/A holotoxin signal was slower, with detection starting at 4-6h. This indicated that the holotoxin alone was sufficient for entry but the presence of NAPs enhanced the rate of entry. Botulinum neurotoxin serotype A detection peaked at approximately 6 and 8h for complex and holotoxin, respectively, and thereafter began to disperse with some toxin remaining in the epithelia after 24h. Purified HA complexes alone were also internalized and followed a similar time course to that of BoNT/A complex internalization. However, recombinant HA complexes did not enhance BoNT/A holotoxin entry in the absence of a physical link with BoNT/A. We propose a model for BoNT/A toxin complex translocation whereby toxin complex entry is facilitated by NAPs in a receptor-mediated mechanism. Understanding the intestinal uptake of BoNT complexes will aid the development of new measures to prevent or treat oral intoxications. |
| وصف الملف: | application/pdf |
| تدمد: | 1462-5822 1462-5814 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fdae4563162af92540359aaf7434c4a6Test https://doi.org/10.1111/cmi.12424Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fdae4563162af92540359aaf7434c4a6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14625822 14625814 |
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