Butyrate induced choleragen receptors

HeLa cells were treated with 5 mM butyrate for 48 h or with 1 yM GM1 for 1 h. Both types of treated cells bound similar amounts of 125I-choleragen and about 60-fold more than did control cells (Fig. 6a). When the cells were exposed to a saturating dose of toxin, the time course and extent of cyclic AMP accumulation were similar for both the butyrate-treated and the GM1-treated HeLa cells and more rapid than in the control cells (Fig. 6b). Thus, butyrate induces choleragen receptors in HeLa cells that are functionally equivalent to those created by incorporation of exogenous GM1. 

Table VIII. Effect of Cycloheximide on Butyrate-Induced Choleragen Receptors In HeLa Cellsa...

Little is known about the function of gangliosides. Gangliosides may serve as cell surface receptors (45) and as biotransducers of membrane-mediated information ). The ganglioside GM1 has been implicated as the receptor for choleragen. Our studies clearly indicate that butyrate induces toxin receptors and GM1 in parallel. In addition, the toxin receptors induced by butyrate are functionally indistinguishable from exogenous GM1 that has been absorbed by the cells. We believe that these observations are the quintessential evidence that GM1 alone is the receptor for choleragen. 

The induction of toxin receptors by butyrate also occurred in serum-free medium (5). Serum contains gangliosides including GM1 and GM1-deficient cells can absorb GM1 from serum and become responsive to choleragen (22). Cells exposed simultaneously to butyrate and cyc1oheximide""cTid not exhibit an increase in choleragen binding (unpublished observations). Thus, butyrate appears to induce toxin receptors de novo in a manner analogous to the induction of GM3. 

Several other cultured cell lines were affected by butyrate (5). These included rat glial C6 cells (12-fold increase) and Friend erythroleukemic cells (4-fold increase). The increase in choleragen receptors in Friend cells was also time dependent (Table III). In addition, butyrate appeared to be specific dimethyl-sulfoxide (DMSO) induces erythroid differentiation (23) as does butyrate (24) but it did not cause an increase in toxin receptors (Table 111)7... 

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