Document Detail


Soapwort saponins trigger clathrin-mediated endocytosis of saporin, a type I ribosome-inactivating protein.
MedLine Citation:
PMID:  18775419     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
A Weng; C Bachran; H Fuchs; M F Melzig
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-08-15
Journal Detail:
Title:  Chemico-biological interactions     Volume:  176     ISSN:  1872-7786     ISO Abbreviation:  Chem. Biol. Interact.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-11-10     Completed Date:  2009-01-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0227276     Medline TA:  Chem Biol Interact     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  204-11     Citation Subset:  IM    
Affiliation:
Institute of Pharmacy, Free University Berlin, D-14195 Berlin, Germany.
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MeSH Terms
Descriptor/Qualifier:
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:
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

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