We previously demonstrated that weak electric current (WEC) induces the skin penetration of macromolecules by the cleavage of intercellular junctions and allows for incorporation of macromolecules into cells via endocytosis. We further showed that WEC facilitates the leakage of macromolecules from endosomes to cytoplasm and that this phenomenon correlates with increased endosomal ceramide levels. From these observations, it suggested ceramide production is induced by WEC. In this study, to investigate mechanisms by which WEC treatment increases ceramide levels, acyl chains in ceramides of WEC-treated cells were analyzed. As a result, we found that WEC increased the amounts of C16:0, C22:0, and C24:1 ceramides and that WEC induced ceramide synthase 2 expression. Therefore, we conclude that WEC activates the ceramide synthesis pathway and that increased endosomal ceramide would contribute to the leakage of macromolecules.
Keywords: weak electric current, ceramide synthesis, cytoplasmic delivery
