Induction of mitochondrial Apo2.7 molecules and generation of reactive oxygen-intermediates in cultured lymphocytes by the toxic proteins from Viscumalbum L.

We analysed mitochondrial alterations in human lymphocytes incubated with t oxins exerting RNA and/or protein synthesis/transport inhibitory activity. We found that all toxins known to affect macromolecule synthesis, such as r icin from Ricinus communis, mistletoe lectin I (ML I) from Viscum album, cy cloheximide, actinomycin D, and brefeldin A but also the thionins from Visc um album (viscotoxins; VT) generated reactive oxygen intermediates (ROI) an d induced expression of newly described mitochondrial membrane proteins Apo 2.7, however, with different kinetics. Apart from a rapid permeabilisation of cell membranes by the VT with swelling of mitochondria, loss of their cr istae and ROI generation within 2-4 h, the majority of the cells may have r eceived a distinct 'death signal' resulting in an induction of Apo2.7 molec ules within 24 h, In contrast, protein synthesis/transport inhibition may s ignal for apoptosis within 24 h by decreasing distinct 'survival promoters' which remain to be characterised. (C) 1999 Elsevier Science S.A. All right s reserved.