In:
Journal of Pharmacy and Pharmacology, Oxford University Press (OUP), Vol. 62, No. 2 ( 2010-03-19), p. 181-187
Abstract:
Sphingolipids act as structural components in cell membranes, and form lipid intermediates that have functional roles as signalling molecules in various cellular processes. Our previous findings have suggested that sphingolipid metabolites are deeply involved in the regulation of melanogenic processes. In this study we aimed to examine sphingosylphosphorylcholine-mediated signalling pathways related to melanogenesis. Methods We determined the hypopigmenting effects and the related signalling pathways of sphingosylphosphorylcholine in Mel-Ab cells. In particular, we analysed the involvement of the G-protein-coupled receptor in sphingosylphosphorylcholine-induced MITF degradation. Key findings Western blotting revealed that sphingosylphosphorylcholine induced the activation of extracellular signal-regulated kinase (ERK), as well as Akt. Moreover, the specific Akt pathway inhibitor LY294002 blocked the hypopigmenting effect of sphingosylphosphorylcholine and abrogated the sphingosylphosphorylcholine-mediated down-regulation of microphthalmia-associated transcription factor (MITF), showing that the Akt pathway is involved in sphingosylphosphorylcholine-mediated melanin inhibition. Treatment with the proteasome inhibitor MG132 blocked the decrease in MITF by sphingosylphosphorylcholine, but sphingosylphosphorylcholine did not decrease the level of MITF mRNA, indicating that the reduction in the level of MITF results from MITF degradation. Furthermore, pre-incubation of Mel-Ab cells with pertussis toxin completely abolished the hypopigmenting effects and the activation of ERK and Akt by sphingosylphosphorylcholine, suggesting that the effects of sphingosylphosphorylcholine are mainly dependent on the G-protein-coupled receptor). Conclusions Together, these results suggest that sphingosylphosphorylcholine reduces melanin synthesis via pertussis toxin-sensitive ERK and Akt activation, and subsequent MITF degradation.
Type of Medium:
Online Resource
ISSN:
0022-3573
,
2042-7158
DOI:
10.1211/jpp.62.02.0005
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2010
detail.hit.zdb_id:
2041988-0
detail.hit.zdb_id:
2050532-2
SSG:
15,3
