title: The Cytotoxicity of Elderberry Ribosome-Inactivating Proteins Is Not Solely Determined by Their Protein Translation Inhibition Activity.
abstract: Although the protein translation inhibition activity of ribosome inactivating proteins (RIPs) is well documented, little is known about the contribution of the lectin chain to the biological activity of these proteins. In this study, we compared the in vitro and intracellular activity of several S. nigra (elderberry) RIPs and non-RIP lectins. Our data demonstrate that RIPs from elderberry are much more toxic to HeLa cells than to primary fibroblasts. Differences in the cytotoxicity between the elderberry proteins correlated with differences in glycan specificity of their lectin domain, cellular uptake efficiency and intracellular destination. Despite the fact that the bulk of the RIPs accumulated in the lysosomes and partly in the Golgi apparatus, we could demonstrate effective inhibition of protein synthesis in cellula. As we also observed cytotoxicity for non-RIP lectins, it is clear that the lectin chain triggers additional pathways heralding cell death. Our data suggest that one of these pathways involves the induction of autophagy.
authors.affiliation: Department of Molecular Biotechnology, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium.
authors.forename: Chenjing
authors.initials: C
authors.lastname: Shang
authors.affiliation: Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, South Kensington Campus, London, United Kingdom.
authors.forename: Qiushi
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, South Kensington Campus, London, United Kingdom.
authors.forename: Anne
authors.initials: A
authors.lastname: Dell
authors.affiliation: Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, South Kensington Campus, London, United Kingdom.
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Haslam
authors.affiliation: Department of Molecular Biotechnology, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium; Department Veterinary Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Antwerp, Belgium.
authors.forename: Winnok H
authors.initials: WH
authors.lastname: De Vos
authors.affiliation: Department of Molecular Biotechnology, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium.
authors.forename: Els J M
authors.initials: EJ
authors.lastname: Van Damme
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D037121:Plant Lectins / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects*; D054788:Ribosome Inactivating Proteins / Q000494:pharmacology*; D027924:Sambucus nigra
chemical_list: D037121:Plant Lectins; C050600:Sambucus nigra lectins; D054788:Ribosome Inactivating Proteins