| Soapwort saponins trigger clathrin-mediated endocytosis of saporin, a type I ribosome-inactivating protein. | |
MedLine Citation:
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PMID: 18775419 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Saporin, a type I ribosome-inactivating protein (RIP), removes adenine residues from the 28S ribosomal RNA as part of a process that leads to inhibition of protein synthesis. However, as shown in this study, neither saporin nor his-tagged saporin (both 0.6-6 pM) exert toxicity on several human cell lines including H-2171, SK-N-SH, HEP-G2, MOLT-3, THP-1, HL-60 and ECV-304. Saporin and his-tagged saporin became highly cytotoxic when they were used in a combined treatment with Soapwort saponins (SA). When combined with SA (2-4 microg/ml) saporin became as cytotoxic as the highly toxic type II RIP rViscumin reflected by an IC50 of 42.5x10(-12) M for saporin and 21.5x10(-12) M for rViscumin. We demonstrated that saporin was internalized via clathrin-mediated endocytosis, followed by the release into the endosomal transport system. Our results indicate that SA triggers this endocytic event rendering the otherwise cell membrane impermeable type I RIP saporin a potent cytotoxin. This effect was not cell line-specific suggesting that saporin exploits a common SA-dependent mechanism to enter cells. |
Authors:
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A Weng; C Bachran; H Fuchs; M F Melzig |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-08-15 |
Journal Detail:
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Title: Chemico-biological interactions Volume: 176 ISSN: 1872-7786 ISO Abbreviation: Chem. Biol. Interact. Publication Date: 2008 Nov |
Date Detail:
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Created Date: 2008-11-10 Completed Date: 2009-01-21 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0227276 Medline TA: Chem Biol Interact Country: Ireland |
Other Details:
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Languages: eng Pagination: 204-11 Citation Subset: IM |
Affiliation:
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Institute of Pharmacy, Free University Berlin, D-14195 Berlin, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Membrane
/
drug effects,
metabolism Cell Membrane Permeability / drug effects Cell Survival / drug effects Cells, Cultured Chlorpromazine / pharmacology Clathrin / metabolism* Cyclosporine / pharmacology Dose-Response Relationship, Drug Endocytosis / drug effects* Endosomes / drug effects, metabolism Filipin / pharmacology Humans Imipramine / pharmacology Macrolides / pharmacology Microscopy, Fluorescence Microtubules / drug effects, metabolism Nocodazole / pharmacology Okadaic Acid / pharmacology Recombinant Proteins / antagonists & inhibitors, pharmacology Ribosome Inactivating Proteins, Type 1 / chemistry, metabolism*, toxicity Ribosome Inactivating Proteins, Type 2 / pharmacology Ribosomes / drug effects, metabolism Saponins / pharmacology* Toxins, Biological / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Clathrin; 0/Macrolides; 0/Recombinant Proteins; 0/Ribosome Inactivating Proteins, Type 1; 0/Ribosome Inactivating Proteins, Type 2; 0/Saponins; 0/Toxins, Biological; 0/mistletoe lectin I; 31430-18-9/Nocodazole; 480-49-9/Filipin; 50-49-7/Imipramine; 50-53-3/Chlorpromazine; 59865-13-3/Cyclosporine; 78111-17-8/Okadaic Acid; 88899-55-2/bafilomycin A1; EC 3.2.2.22/saporin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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