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Inhibition of DNA Synthesis in C 6 Glioma Cells Following Cellular Incorporation of GM1 Ganglioside and Choleragenoid Exposure
Author(s) -
Skaper Stephen D.,
Facci Laura,
Favaron Marco,
Leon Alberta
Publication year - 1988
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1988.tb01799.x
Subject(s) - ganglioside , dna synthesis , cholera toxin , protein subunit , microbiology and biotechnology , biology , thymidine , cell culture , cell growth , dna , biochemistry , fibroblast , glioma , in vitro , gene , endocrinology , cancer research , genetics
The B subunit of cholera toxin, which is multiva‐lent and binds specifically to GM1 ganglioside on the cell surface, has previously been used as a ganglioside‐specific probe to regulate DNA synthesis in thymocytes and fibro‐blasts. To explore in more detail this growth‐regulatory action of gangliosides, C 6 glioma cells (which are GM1 ganglioside deficient) were used as a model system. When cultures of C 6 cells were first treated with GM1, followed by exposure to the B subunit, proliferation was inhibited, as measured by 3 H‐labeled thymidine incorporation into DNA. Pretreatment of the cells with 50 μ M GM1 for 15 min (followed by washing with fetal calf serum) and incubation with 1 μ/ml of B subunit for 21 h was sufficient to reduce DNA synthesis to 15% of control values (and confirmed by autoradiographic analysis), although maximal inhibition could be achieved with as little as 30 min exposure to B, followed by washing. Furthermore, the B subunit inhibited the response of the C 6 cells to basic fibroblast growth factor only following GM1 pretreatment. The B subunit‐induced inhibition of DNA synthesis was specific for the ganglioside GM 1 , and was unrelated to increases of cyclic AMP. These results demonstrate that cell‐incorporated GM1 ganglioside may act as a receptor capable of undergoing a specific ligand interaction, subsequently affecting molecular processes at the nuclear level.