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Selected Publication:

Type of publication: Journal Article
Type of document: Full Paper

Year: 2004

Authors: Sun, J; Pohl, EE; Krylova, OO; Krause, E; Agapov, II; Tonevitsky, AG; Pohl, P

Title: Membrane destabilization by ricin.

Source: Eur Biophys J. 2004; 33(7):572-579



Authors Vetmeduni Vienna:

Pohl Elena


Abstract:
Ricin is a promising candidate for the treatment of cancer because it can be selectively targeted to tumor cells via linkage to monoclonal antibodies. Biochemical evidence suggests that escape of ricin or its ribosome-inactivating subunit from an intracellular compartment is mediated by retrograde transport to the endoplasmic reticulum and subsequent direction into the ER-associated degradation pathway. Alternatively, lipase activity of ricin may facilitate leakage from endocytic vesicles. We have observed ricin-mediated release of macromolecular dyes from lipid vesicles that mimic the composition of endosomal membranes. Release of small molecules occurs to the same extent, suggesting an all-or-none mechanism due to bilayer destabilization. The level of accompanying membrane fusion depends on vesicle composition. Since it takes 24 h of incubation before the first traces of lysolipids are detectable by matrix-assisted laser desorption/ionization mass spectrometry, membrane destabilization is not due to the lipase activity of ricin.

Keywords Pubmed: Diffusion
Endosomes/chemistry*
G(M1) Ganglioside/chemistry*
Kinetics
Liposomes/chemistry*
Membrane Fluidity*
Membranes, Artificial
Phosphatidylcholines/chemistry*
Porosity
Ricin/chemistry*
Solutions


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