Korean J Physiol Pharmacol.  2012 Aug;16(4):287-291. 10.4196/kjpp.2012.16.4.287.

Dipeptides Inhibit Melanin Synthesis in Mel-Ab Cells through Down-Regulation of Tyrosinase

• Lee HE
• Kim EH
• Choi HR
• Sohn UD
• Yun HY
• Baek KJ
• Kwon NS
• Park KC
• Kim DS

• KMID: 2011164
• DOI: http://doi.org/10.4196/kjpp.2012.16.4.287

Abstract

This study investigated the effects of proline-serine (PS) and valine-serine (VS) dipeptides on melanogenesis in Mel-Ab cells. Proline-serine and VS significantly inhibited melanin synthesis in a concentration-dependent manner, though neither dipeptide directly inhibited tyrosinase activity in a cell-free system. Both PS and VS down-regulated the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase. In a follow-up study also described here, the effects of these dipeptides on melanogenesis-related signal transduction were quantified. Specifically, PS and VS induced ERK phosphorylation, though they had no effect on phosphorylation of the cAMP response element binding protein (CREB). These data suggest that PS and VS inhibit melanogenesis through ERK phosphorylation and subsequent down-regulation of MITF and tyrosinase. Properties of these dipeptides are compatible with application as skin-whitening agents.

Keyword

Dipeptide; ERK; Melanogenesis; MITF; Tyrosinase

MeSH Terms

Cell-Free System
Cyclic AMP Response Element-Binding Protein
Dipeptides
Down-Regulation
Follow-Up Studies
Melanins
Microphthalmia-Associated Transcription Factor
Monophenol Monooxygenase
Phosphorylation
Signal Transduction
Cyclic AMP Response Element-Binding Protein
Dipeptides
Melanins
Microphthalmia-Associated Transcription Factor
Monophenol Monooxygenase

Figure

• 

  Fig. 1 Effects of PS and VS on Mel-Ab cell viability. Mel-Ab cells were treated with PS (A) or VS (B) at 1~50 µg/ml for 24 h. Cell viability was determined using a crystal violet assay as described in Methods. All data were expressed as the mean±S.D. of triplet viability assays.

• 

  Fig. 2 Effects of PS and VS on melanogenesis in Mel-Ab cells. Mel-Ab cells were treated with PS or VS at 1~20 µg/ml for 4 days. (A) Phase contrast photographs were taken using a digital video camera. Melanin content (B and C) and tyrosinase activity (D and E) were measured as described in Methods. Data are expressed as the mean±S.D. of triplicate assays. **p<0.01 compared to the untreated control.

• 

  Fig. 3 The dipeptides PS and VS downregulate MITF and tyrosinase expression in Mel-Ab cells. Mel-Ab cells were treated with PS (A) or VS (B) (20 µg/ml) for the times indicated. Western blot analyses were performed with MITF- and tyrosinase-specific antibodies. Equal protein loading was confirmed by probing for actin expression.

• 

  Fig. 4 Effects of PS and VS on melanogenesis-related signaling. Mel-Ab cells were treated with PS (A) or VS (B) (20 µg/ml) for 0~360 min, after which the whole cell lysates were analyzed by western blotting using antibodies specific for phospho-ERK and phospho-CREB. Equal protein loading was confirmed by probing for actin expression.

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