Abstract
BackgroundSphingosylphosphorylcholine (SPC) acts as a potent lipid mediator and signaling molecule in various cell types. In the present study, we investigated the effects of SPC on melanogenesis and SPC-modulated signaling pathways related to melanin synthesis.MethodsMelanin production was measured in Mel-Ab cells. A luciferase assay was used to detect transcriptional activity of the MITF promoter. Western blot analysis was performed to examine SPC-induced signaling pathways.ResultsSPC produced significant hypopigmentation effects in a dose-dependent manner. It was found that SPC induced not only activation of Akt but also stimulation of mTOR, a downstream mediator of the Akt signaling pathway. Moreover, SPC decreased the levels of LC3 II, which is known to be regulated by mTOR. Treatment with the mTOR inhibitor rapamycin eliminated decreases in melanin and LC3 II levels by SPC. Furthermore, we found that the Akt inhibitor LY294002 restored SPC-mediated downregulation of LC3 II and inhibited the activation of mTOR by SPC.ConclusionsOur data suggest that the mTOR signaling pathway is involved in SPC-modulated melanin synthesis.
Highlights
Sphingosylphosphorylcholine (SPC) acts as a potent lipid mediator and signaling molecule in various cell types
Microphthalmia-associated transcription factor (MITF) is a critical factor in melanin synthesis because it modulates the expression of tyrosinase, tyrosinaserelated protein 1 (TRP1), and TRP2 [4,5]
Effects of SPC on melanin synthesis and tyrosinase activity in Mel-Ab cells We previously reported that SPC suppresses melanin production in normal human melanocytes [20]
Summary
Sphingosylphosphorylcholine (SPC) acts as a potent lipid mediator and signaling molecule in various cell types. We investigated the effects of SPC on melanogenesis and SPC-modulated signaling pathways related to melanin synthesis. Tyrosinase catalyses the first 2 ratelimiting steps of melanogenesis, whereas tyrosinaserelated protein 1 (TRP1) and TRP2 convert melanin into different types. Microphthalmia-associated transcription factor (MITF) is a critical factor in melanin synthesis because it modulates the expression of tyrosinase, TRP1, and TRP2 [4,5]. It has been reported that several signaling pathways are involved in regulating melanin synthesis. The extracellular signal-regulated kinase (ERK) signaling pathway induces the inhibition of melanin synthesis in mouse B16 melanoma cells [6]. LY294002, a specific inhibitor of the Akt pathway, triggers melanogenesis in B16 cells [10]. The activation of Akt is implicated in modulating melanogenesis [11]
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