Sphingosylphosphorylcholine is a Melanogenic Stimulator for Human Melanocytes.
As lysosphingolipids have multiple bio-modulator functions in various types of cells, we measured the biological effects of sphingosylphosphorylcholine (SPC) on cultured human melanocytes to determine whether these lysosphingolipids have the potential to activate these cells. The addition of SPC to cultured human melanocytes significantly stimulated DNA synthesis assessed by [3H]thymidine and melanogenesis assessed by the release of [3H]H2O (tyrosinase activity), the incorporation of [14C]thiouracil (melanin synthesis) and dopa-oxidase activity. Reverse transcription-polymerase chain reaction of RNA isolated from human melanocytes exposed to SPC revealed an upregulation of mRNA transcripts for tyrosinase, microphthalmia-associated transcription factor-M, endothelin B receptor and the stem cell factor receptor, c-kit. An increase in expression of tyrosinase and c-kit proteins was also demonstrated by Western blot analysis. This stimulation of melanogenesis by SPC was associated with a marked increase in the phosphorylation of extracellular signal-regulated kinase 1/2. These results suggest that SPC may be a melanogenic stimulator of human melanocytes inducing the coordinated upregulated expression of various melanogenic molecules, including c-kit.
Higuchi
Kazuhiko
K
Department of Dermatology, Tokyo Women's Medical University, Tokyo, Japan.
Kawashima
Makoto
M
Ichikawa
Yoshiaki
Y
Imokawa
Genji
G
D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D008543:Melanins / Q000378:metabolism*; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051739:Microphthalmia-Associated Transcription Factor; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D010766:Phosphorylation; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017466:Receptors, Endothelin / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019089:Stem Cell Factor / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D004268:DNA-Binding Proteins; C497234:MITF protein, human; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D012333:RNA, Messenger; D017466:Receptors, Endothelin; D019089:Stem Cell Factor; D014157:Transcription Factors; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D014442:Monophenol Monooxygenase; D019009:Proto-Oncogene Proteins c-kit; D020928:Mitogen-Activated Protein Kinases; D013110:Sphingosine