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An extract of Melia toosendan attenuates endothelin-1-stimulated pigmentation in human epidermal equivalents through the interruption of PKC activity within melanocytes

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An Erratum to this article was published on 12 April 2013

Abstract

To elucidate the effects of redox balance regulation on epidermal pigmentation, we used an antioxidant-rich extract of the herb Melia toosendan (dried mature fruits) to assess its effect on endothelin-1 (EDN1)-stimulated pigmentation in human epidermal equivalents and analyzed its biological mechanism of action. Addition of the Melia toosendan extract elicited a marked depigmenting effect on EDN1-stimulated pigmentation after 14 days of treatment, which was accompanied by a significant decrease in eumelanin content. Real-time RT-PCR and Western blotting revealed that the EDN1-stimulated expression of melanocyte-specific proteins (including tyrosinase) was significantly suppressed at the gene and protein levels by the extract. Signaling analysis with specific inhibitors and immunoblots revealed that in melanoma cells treated with the extract, there was a marked deficiency in the EDN1-stimulated phosphorylation of Raf-1, MEK, ERK, MITF and CREB. Since all those proteins are downstream phosphorylation targets of PKC activity, these findings indicate that the Melia toosendan extract attenuates the EDN1-stimulated pigmentation by preferentially inhibiting PKC activity within melanocytes.

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Abbreviations

EDN1:

Endothelin-1

EDNRB:

Endothelin B receptor

IL:

Interleukin

MAPK:

Mitogen-activated protein kinase

MITF:

Microphthalmia-associated transcription factor

NHM:

Normal human melanocytes

PKA:

Protein kinase A

PKC:

Protein kinase C

ROS:

Reactive oxygen species

SCF:

Stem cell factor

TRP-1:

Tyrosinase-related proteins-1/2

Dct:

Dopachrome tautomerase

TYK:

Tyrosine kinase

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Acknowledgments

We appreciate Dr. Hiroshi Murata in the Department of Dermatology, School of Medicine, Shinshu University for providing us with acral lentigo malignant melanoma (SM2-1) cells.

Conflict of interest

None.

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Authors and Affiliations

  1. School of Bioscience and Biotechnology, Tokyo University of Technology, 1404-1 Katakura, Hachioji, Tokyo, 192-0982, Japan

    Hiroaki Nakajima, Yuki Wakabayashi & Genji Imokawa

  2. School of Health Sciences, Fujita Health University, Toyoake, Japan

    Kazumasa Wakamatsu

Authors
  1. Hiroaki Nakajima
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  2. Yuki Wakabayashi
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  3. Kazumasa Wakamatsu
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  4. Genji Imokawa
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Corresponding author

Correspondence to Genji Imokawa.

Additional information

An erratum to this article is available at http://dx.doi.org/10.1007/s00403-013-1350-9.

Electronic supplementary material

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Supplementary material 1 (DOCX 21 kb)

Inhibitory effect of the

Melia toosendanextract on EDN1-stimulated pigmentation in human epidermal equivalents over 14 days of culture. Human epidermal equivalents were cultured at 37˚C for 14 days in DMEM supplemented with 10 nMEDN1, with or without the Melia toosendan extract at concentrations of 2, 5 or10 µg/ml. The media were exchanged every 2 days (TIFF 743 kb)

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Supplementary material 8 (TIFF 278 kb)

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Nakajima, H., Wakabayashi, Y., Wakamatsu, K. et al. An extract of Melia toosendan attenuates endothelin-1-stimulated pigmentation in human epidermal equivalents through the interruption of PKC activity within melanocytes. Arch Dermatol Res 303, 263–276 (2011). https://doi.org/10.1007/s00403-011-1143-y

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  • DOI: https://doi.org/10.1007/s00403-011-1143-y

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