Effect of gangliosides Gm1 and Gm3 on the binding, internalization and cytotoxic activity of ricin
Tonevitskiĭ, A.G.; Zhukova, O.S.; Timofeeva, N.V.; Bergel'son, L.D.
Molekuliarnaia Biologiia 21(6): 1694-1701
1987
ISSN/ISBN: 0026-8984 PMID: 3447055 Document Number: 287620
Treatment of Burkitt lymphoma EB-3 cells with gangliosides Gm1 and Gm3 results in their binding and partial incorporation into the cell membrane. Up to 25% of the bound ganglioside Gm1 can interact with the B-subunit of ricin, inducing the 3-times increase in ricin binding by the cells treated with 0.2 mM ganglioside Gm1. Increase in the number of ricin binding sites leads, however, not to the enhancement of the cytotoxic effect of ricin, as it might be expected, but to its decrease. The similar protective effect has been observed for the cells treated with ganglioside Gm3. On the other side, the 20-times increase in ricin binding by the cells, treated with neuroaminidase correlates with the 6-times enhancement of its cytotoxic effect. It has been shown that after a 20 min incubation at 37.degree. C 15 and 35% of bound ricin can be revealed on the surface of the intact cells and the cells treated with ganglioside Gm1, respectively. After a 60 min incubation approximately 10% of the toxin can be revealed on the surface of both types of cells. The different rate of endocytosis may probably explain the differences in the cytotoxic effect of ricin on intact and treated with gangliosides lymphoma cells. The results of this study have been compared with the data on the existence of the two populations of ricin binding sites on the surface of EB-3 cells obtained earlier. The suggestion has been made that only the high-affinity receptors (1% of the total number of binding sites) are responsible for the cytotoxic effect of ricin.