1-Oleoyl-2-Acetylglycerol and A23187 Potentiate Axolemma-and Myelin-Induced Schwann Cell Proliferation

The effects of 1-oleoyl-2-acetylglycerol (OAG) and the calcium ionophore A23187 on the proliferation of Schwann cells stimulated with either a myelin-enriched membrane fraction (MEF) or an axolemma-enriched membrane fraction (AEF) have been examined. Using incorporation of [3H]thymidine as an index of proliferation, 16% of the cells became labeled after incubation with MEF (20 micrograms protein/ml) and AEF (40 micrograms protein/ml) for 72 h. Only 0.5% of the cells became labeled in cultures which were not exposed to the membrane fractions. Addition of OAG (10-500 microM) or A23187 (1.9-190 nM) in the absence of the membrane mitogens had no effect on the proliferative response of quiescent cultures of Schwann cells. When added simultaneously, however, OAG and A23187 were able to induce proliferation of the cells, although the response was only 30% of the response achieved with maximal doses of either AEF or MEF. Both OAG and A23187 were able to potentiate the mitogenicity of AEF or MEF, but only when AEF and MEF were added at submaximal concentrations. When Schwann cells were prelabeled with [3H]glycerol and then stimulated to proliferate with AEF or MEF, the amount of [3H]diacylglycerol was increased two- to threefold above that in control cultures for time periods up to 1 h. These results suggest that the proliferation of Schwann cells induced by either AEF or MEF is partially mediated through the combined effects of diacylglycerol and an increase in intracellular calcium.