Involvement of mTOR signaling in sphingosylphosphorylcholine-induced hypopigmentation effects.

Abstract

BACKGROUND:

Sphingosylphosphorylcholine (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.

METHODS:

Melanin 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.

RESULTS:

SPC 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.

CONCLUSIONS:

Our data suggest that the mTOR signaling pathway is involved in SPC-modulated melanin synthesis.

• Authors: Hyo-Soon Jeong, Seung Hoon Lee, Hye-Young Yun, Kwang Jin Baek, Nyoun Soo Kwon, Kyoung-Chan Park, Dong-Seok Kim
• Journal: Journal of biomedical science (J Biomed Sci) Vol. 18 Pg. 55 (Aug 13 2011) ISSN: 1423-0127 [Electronic] England
• PMID: 21838918 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chromones
• Melanins
• Morpholines
• sphingosine phosphorylcholine
• Phosphorylcholine
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• Luciferases
• Monophenol Monooxygenase
• mTOR protein, mouse
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases
• Sphingosine
• Sirolimus

Topics

• Analysis of Variance
• Animals
• Blotting, Western
• Cell Line
• Chromones (pharmacology)
• Dose-Response Relationship, Drug
• Hypopigmentation (chemically induced, metabolism)
• Luciferases
• Melanins (biosynthesis)
• Mice
• Microscopy, Phase-Contrast
• Monophenol Monooxygenase (metabolism)
• Morpholines (pharmacology)
• Phosphorylcholine (analogs & derivatives, pharmacology, toxicity)
• Proto-Oncogene Proteins c-akt (antagonists & inhibitors, metabolism)
• Signal Transduction (physiology)
• Sirolimus (pharmacology)
• Sphingosine (analogs & derivatives, pharmacology, toxicity)
• TOR Serine-Threonine Kinases (metabolism)
• Transfection