Effect of dimethyl sulfoxide on transformed rat Schwann cells

Cultured rat Schwann cells transformed by Simian Virus 40 (SV40) have previously been shown to retain their ability to synthesize myelin-associated galactosylceramide and sulfatide. Little is known about the mechanism regulating galactosphingolipid synthesis in Schwann cells. We have found that growing the transformed Schwann cells in the presence of dimethyl sulfoxide (DMSO) markedly inhibits the incorporation of [35S]sulfate into sulfatide, in a time- and dose-dependent manner. The concentration of DMSO which resulted in a half-maximal inhibition after 6 days of incubation was 0.5%, and the incubation time required for a half-maximal effect at 1.0% DMSO was approximately 4 days. In contrast, DMSC did not affect the incorporation of [35S]sulfate into glycosaminoglycans. In addition, DMSO treatment has little effect on the synthesis of cellular DNA, proteins and lipids. When transformed Schwann cells were treated with DMSO, a substantial decrease in the incorporation of [3H]galactose into galactosylceramide was observed. The concentration of DMSO which resulted in a half-maximal inhibition of galactosylceramide synthesis was approximately 0.5%, similar to the concentration required for a similar effect on sulfatide synthesis. However, the incubation time required for a half-maximal inhibitory effect on galactosylceramide synthesis at 1.0% DMSO was less than 1 day, which was substantially shorter than the time required for the inhibition of sulfatide synthesis at this concentration. This finding is consistent with the interpretation that treatment with DMSO inhibits the synthesis of galactosylceramide, a precursor of sulfatide, which results in a decrease in the synthesis of sulfatide during a prolonged incubation of DMSO.