Lanthionine Ketimine Ethyl Ester Induces Proliferation and Maturation and Regulates Calcium Flux in Primary Mouse Oligodendrocyte Progenitor Cells.

Previous studies have shown that lanthionine ketimine ethyl ester (LKE), a semi-synthetic derivative of the endogenous amino acid lanthionine, can induce proliferation and maturation of oligodendrocyte progenitor cells (OPCs) in vivo. In the current study, we examined the effects of LKE on Ca influx in primary mouse OPCs, as intracellular Ca can regulate those processes. Treatment with LKE stimulated proliferation of OPCs and increased the number of Olig2+, CC1+, and PLP+ cells. LKE also reduced cell death (caspase-3 expressing cells). Measurements of Ca flux showed that LKE increased basal Ca levels, reduced Ca influx following stimulation with glutamate or ATP, and increased Ca flux because of depolarization with KCl. Reduced Ca responses were also observed following treatment with a peptide that disrupts interactions of collapsin response mediated protein 2 (CRMP2), a primary target of LKE. These findings demonstrate regulation of Ca levels in OPCs by LKE and suggest that these actions may be mediated, in part, by CRMP2. LKE or related analogs could therefore be of benefit for the treatment of multiple sclerosis as well as other demyelinating conditions.