Ceramide Inhibits Cell Proliferation through Akt/PKB Inactivation and Decreases Melanin Synthesis in Mel‐Ab Cells
2001; Wiley; Volume: 14; Issue: 2 Linguagem: Inglês
10.1034/j.1600-0749.2001.140206.x
ISSN1600-0749
AutoresDONG‐SEOK KIM, SOOK‐YOUNG KIM, Seong-Joon Moon, JIN‐HO CHUNG, Kyu-Han Kim, KWANG‐HYUN CHO, Kyoung‐Chan Park,
Tópico(s)Cholesterol and Lipid Metabolism
ResumoCeramide is a bioactive sphingolipid that mediates a variety of cell functions. However, the effects of ceramide on cell growth and the melanogenesis of melanocytes are not known. In the present study, we investigated the actions of cell‐permeable ceramide and its possible role in the signaling pathway of a spontaneously immortalized mouse melanocyte cell line, Mel‐Ab. Our results show that C 2 ‐ceramide inhibits DNA synthesis in Mel‐Ab cells and G361 human melanoma cells in a dose‐dependent manner. Cell cycle analysis confirmed the inhibition of DNA synthesis by a reduction in the S phase. To investigate the ceramide signaling pathway, we studied whether C 2 ‐ceramide is able to influence extracellular signal‐regulated kinase (ERK) and/or Akt/protein kinase B (PKB) activation. We demonstrated that phosphorylated Akt/PKB is decreased by C 2 ‐ceramide, whereas phosphorylated ERK was only slightly affected. Therefore, the C 2 ‐ceramide‐induced inactivation of Akt/PKB may be closely related to the reduced cell proliferation of Mel‐Ab cells. Furthermore, we assessed the effects of C 2 ‐ceramide on the pigmentation of Mel‐Ab cells. The results obtained showed that the melanin content of cells was significantly reduced by C 2 ‐ceramide at concentrations in the range of 1–10 μM, and that the pigmentation‐inhibiting effect of C 2 ‐ceramide is much greater than that of kojic acid at 1–100 μM. In addition, we found that the activity of tyrosinase is reduced by C 2 ‐ceramide treatment. Our results demonstrate that C 2 ‐ceramide reduces the pigmentation of Mel‐Ab cells by inhibiting tyrosinase activity.
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