Induction of mitochondrial Apo2.7 molecules and generation of reactive oxygen-intermediates in cultured lymphocytes by the toxic proteins from Viscum album L.
We analysed mitochondrial alterations in human lymphocytes incubated with toxins exerting RNA and/or protein synthesis/transport inhibitory activity. We found that all toxins known to affect macromolecule synthesis, such as ricin from Ricinus communis, mistletoe lectin I (ML I) from Viscum album, cycloheximide, actinomycin D, and brefeldin A but also the thionins from Viscum album (viscotoxins; VT) generated reactive oxygen intermediates (ROI) and induced expression of newly described mitochondrial membrane proteins Apo2.7, however, with different kinetics. Apart from a rapid permeabilisation of cell membranes by the VT with swelling of mitochondria, loss of their cristae and ROI generation within 2-4 h, the majority of the cells may have received a distinct 'death signal' resulting in an induction of Apo2.7 molecules within 24 h. In contrast, protein synthesis/transport inhibition may signal for apoptosis within 24 h by decreasing distinct 'survival promotors' which remain to be characterised.
Krebsforschung Herdecke, Department of Applied Immunology, University of Witten/Herdecke, Communal Hospital Herdecke, Germany. arbuess@t-online.de
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Büssing
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Wagner
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Wagner
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Stein
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Schietzel
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Schaller
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Pfüller
D017304:Annexin A5 / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D007700:Kinetics; D008214:Lymphocytes / Q000187:drug effects*; D008565:Membrane Proteins / Q000378:metabolism*; D014784:Mistletoe / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism; D010940:Plant Proteins; D010946:Plants, Medicinal; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013997:Time Factors; D014118:Toxins, Biological / Q000494:pharmacology*
D017304:Annexin A5; D000903:Antibiotics, Antineoplastic; D008565:Membrane Proteins; D010718:Phosphatidylserines; D010940:Plant Proteins; D017382:Reactive Oxygen Species; D014118:Toxins, Biological; D003609:Dactinomycin; C488038:viscotoxin