Metabolism of melatonin and biological activity of intermediates of melatoninergic pathway in human skin cells

Tae Kang Kim, Konrad Kleszczynśki, Zorica Janjetovic, Trevor Sweatman, Zongtao Lin, Wei Li, Russel J. Reiter, Tobias W. Fischer, Andrzej T. Slominski

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Indolic and kynuric pathways of skin melatonin metabolism were monitored by liquid chromatography mass spectrometry in human keratinocytes, melanocytes, dermal fibroblasts, and melanoma cells. Production of 6-hydroxymelatonin [6(OH)M], N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and 5-methoxytryptamine (5-MT) was detected in a cell type-dependent fashion. The major metabolites, 6(OH)M and AFMK, were produced in all cells. Thus, in immortalized epidermal (HaCaT) keratinocytes, 6(OH)M was the major product with Vmax, 63.7 ng/106 cells and Km, 10.2 μM, with lower production of AFMK and 5-MT. Melanocytes, keratinocytes, and fibroblasts transformed melatonin primarily into 6(OH)M and AFMK. In melanoma cells, 6(OH)M and AFMK were produced endogenously, a process accelerated by exogenous melatonin in the case of AFMK. In addition, N-acetylserotonin was endogenously produced by normal and malignant melanocytes. Metabolites showed selective antiproliferative effects on human primary epidermal keratinocytes in vitro. In ex vivo human skin, both melatonin and AFMK-stimulated expression of involucrin and keratins-10 and keratins-14 in the epidermis, indicating their stimulatory role in building and maintaining the epidermal barrier. In summary, the metabolism of melatonin and its endogenous production is cell type-dependent and expressed in all three main cell populations of human skin. Furthermore, melatonin and its metabolite AFMK stimulate differentiation in human epidermis, indicating their key role in building the skin barrier.

Original languageEnglish (US)
Pages (from-to)2742-2755
Number of pages14
JournalFASEB Journal
Volume27
Issue number7
DOIs
StatePublished - Jul 1 2013

Fingerprint

Melatonin
Bioactivity
Metabolism
Skin
Metabolites
5-Methoxytryptamine
Keratinocytes
Melanocytes
Fibroblasts
Keratin-10
Keratin-14
Epidermis
Melanoma
Liquid chromatography
Mass spectrometry
Cells
6-hydroxymelatonin
Liquid Chromatography
Mass Spectrometry
Population

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Kim, T. K., Kleszczynśki, K., Janjetovic, Z., Sweatman, T., Lin, Z., Li, W., ... Slominski, A. T. (2013). Metabolism of melatonin and biological activity of intermediates of melatoninergic pathway in human skin cells. FASEB Journal, 27(7), 2742-2755. https://doi.org/10.1096/fj.12-224691

Metabolism of melatonin and biological activity of intermediates of melatoninergic pathway in human skin cells. / Kim, Tae Kang; Kleszczynśki, Konrad; Janjetovic, Zorica; Sweatman, Trevor; Lin, Zongtao; Li, Wei; Reiter, Russel J.; Fischer, Tobias W.; Slominski, Andrzej T.

In: FASEB Journal, Vol. 27, No. 7, 01.07.2013, p. 2742-2755.

Research output: Contribution to journalArticle

Kim, TK, Kleszczynśki, K, Janjetovic, Z, Sweatman, T, Lin, Z, Li, W, Reiter, RJ, Fischer, TW & Slominski, AT 2013, 'Metabolism of melatonin and biological activity of intermediates of melatoninergic pathway in human skin cells', FASEB Journal, vol. 27, no. 7, pp. 2742-2755. https://doi.org/10.1096/fj.12-224691
Kim, Tae Kang ; Kleszczynśki, Konrad ; Janjetovic, Zorica ; Sweatman, Trevor ; Lin, Zongtao ; Li, Wei ; Reiter, Russel J. ; Fischer, Tobias W. ; Slominski, Andrzej T. / Metabolism of melatonin and biological activity of intermediates of melatoninergic pathway in human skin cells. In: FASEB Journal. 2013 ; Vol. 27, No. 7. pp. 2742-2755.
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AU - Reiter, Russel J.

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AB - Indolic and kynuric pathways of skin melatonin metabolism were monitored by liquid chromatography mass spectrometry in human keratinocytes, melanocytes, dermal fibroblasts, and melanoma cells. Production of 6-hydroxymelatonin [6(OH)M], N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and 5-methoxytryptamine (5-MT) was detected in a cell type-dependent fashion. The major metabolites, 6(OH)M and AFMK, were produced in all cells. Thus, in immortalized epidermal (HaCaT) keratinocytes, 6(OH)M was the major product with Vmax, 63.7 ng/106 cells and Km, 10.2 μM, with lower production of AFMK and 5-MT. Melanocytes, keratinocytes, and fibroblasts transformed melatonin primarily into 6(OH)M and AFMK. In melanoma cells, 6(OH)M and AFMK were produced endogenously, a process accelerated by exogenous melatonin in the case of AFMK. In addition, N-acetylserotonin was endogenously produced by normal and malignant melanocytes. Metabolites showed selective antiproliferative effects on human primary epidermal keratinocytes in vitro. In ex vivo human skin, both melatonin and AFMK-stimulated expression of involucrin and keratins-10 and keratins-14 in the epidermis, indicating their stimulatory role in building and maintaining the epidermal barrier. In summary, the metabolism of melatonin and its endogenous production is cell type-dependent and expressed in all three main cell populations of human skin. Furthermore, melatonin and its metabolite AFMK stimulate differentiation in human epidermis, indicating their key role in building the skin barrier.

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