Effects of Glycogen on Ceramide Production in Cultured Human Keratinocytes via Acid Sphingomyelinase Activation

Glycogen is a highly branched storage polysaccharide found mainly in the liver and the muscles. Glycogen is also present in the skin, but its functional role is poorly understood. Recently, it has been reported that glycogen plays an important role in intracellular signal transduction. In the epidermis of the skin, keratinocytes are the predominant cells that produce ceramide. Ceramides are lipids composed of sphingosine, and prevent water loss, as well as protecting the skin against environmental stressors. In this study, we investigated the effects of glycogen on ceramide production in cultured keratinocytes. Thin-layer chromatography revealed that incubation of keratinocytes with 2 % glycogen enhanced the cellular amount of ceramide NS (ceramide 2) by 3.4-fold compared to the control. We also found that glycogen regulated the mRNA expression levels of signaling molecules of the sphingomyelin-ceramide pathway by quantitative real-time PCR. The activity of sphingomyelinase was also significantly enhanced by 2.5-fold in cultures with 1 % glycogen compared to the control. Moreover, glycogen increased the ATP production by 1.5-fold compared to the control, while glucose did not affect the production. Western blotting showed that phosphorylation of Akt, a cellular signaling molecule, was inhibited in the presence of glycogen in cultured keratinocytes. This study shows that glycogen upregulates the ceramide production pathway from sphingomyelin in epidermal keratinocytes, and provides new insights into the role of glycogen in cellular signal transduction.