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Glycine hydroxamate inhibits tyrosinase activity and melanin contents through downregulating cAMP/PKA signaling pathways

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Abstract

Among the eight amino acid hydroxamates tested, Glycine hydroxamate (GH) was the best inhibitor of mushroom tyrosinase (TYR). With l-tyrosine as substrate, the GH inhibition of the monophenolase activity of the mushroom TYR was noncompetitive. GH decreased not only TYR protein expression, but also melanin content, tyrosinase-related protein (TRP)-1, TRP-2, and microphthalmia-associated transcription factor (MITF) expression in B16F10 melanoma cells while in the presence of α-melanocyte-stimulating hormone (α-MSH). GH also significantly decreased the isobutylmethylxanthine (IBMX)-induced increase in melanin content, which was not prevented by the ERK inhibitor PD98059. These results suggest GH has the potential for use in cosmetic hypopigmentation.

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Abbreviations

AAHs:

Amino acid hydroxamates

TYR:

Tyrosinase

MITF:

Microphthalmia-associated transcription factor

α-MSH:

α-Melanocyte-stimulating hormone

IBMX:

Isobutylmethylxanthine

CREB:

Cyclic AMP response element binding protein

PKA:

Protein kinase A

TRP-1:

Tyrosinase-related protein-1

TRP-2:

Tyrosinase-related protein-2

ERK:

Extracellular signal-regulated kinases

References

  • Ao Y, Park HY, Olaizola-Horn S, Gilchrest BA (1998) Activation of cAMP-dependent protein kinase is required for optimal α-melanocyte-stimulating hormone-induced pigmentation. Exp Cell Res 244:117–124

    Article  CAS  PubMed  Google Scholar 

  • Blaut M, Braune A, Wunderlich S, Sauer P, Schneider H, Glatt H (2006) Mutagenicity of arbutin in mammalian cells after activation by human intestinal bacteria. Food Chem Toxicol 44:1940–1947

    Article  CAS  PubMed  Google Scholar 

  • Briganti S, Camera E, Picardo M (2003) Chemical and instrumental approaches to treat hyperpigmentation. Pigment Cell Res 16:101–110

    Article  PubMed  Google Scholar 

  • Busca R, Ballotti R (2000) Cyclic AMP a key messenger in the regulation of skin pigmentation. Pigment Cell Res 13:60–69

    Article  CAS  PubMed  Google Scholar 

  • Conti M, Beavo J (2007) Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling. Annu Rev Biochem 76:481–511

    Article  CAS  PubMed  Google Scholar 

  • Englaro W, Bertolotto C, Buscà R, Brunet A, Pagès G, Ortonne JP, Ballotti R (1998) Inhibition of the mitogen-activated protein kinase pathway triggers B16 melanoma cell differentiation. J Biol Chem 273:9966–9970

    Article  CAS  PubMed  Google Scholar 

  • Fernandes M, Paniago EB, Carvalho S (1997) Copper (II) mixed ligands complexes of hydroxamic acids with glycine, histamine and histidine. J Braz Chem Soc 8:537–548

    Article  CAS  Google Scholar 

  • Gilchrest BA, Park HY, Eller MS, Yaar M (1996) Mechanisms of Ultraviolet Light-Induced Pigmentation. Photochem Photobiol 63:1–10

    Article  CAS  PubMed  Google Scholar 

  • Halaban R, Pomerantz S, Marshall S, Lambert D, Lerner A (1983) Regulation of tyrosinase in human melanocytes grown in culture. J Cll Biol 97:480–488

    Article  CAS  Google Scholar 

  • Hearing VJ, Ekel T (1976) Mammalian tyrosinase. A comparison of tyrosine hydroxylation and melanin formation. Biochem J 157:549

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hearing VJ, Tsukamoto K (1991) Enzymatic control of pigmentation in mammals. FASEB J 5:2902–2909

    CAS  PubMed  Google Scholar 

  • Hirsch P, Kaplan NO (1961) The conversion of pyridine hydroxamic acids to amides by mouse liver mitochondria. JBiol Chem 236:926–930

    CAS  Google Scholar 

  • Ishikawa M, Kawase I, Ishii F (2007) Combination of amino acids reduces pigmentation in B16F0 melanoma cells. Biol Pharm Bull 30:677–681

    Article  CAS  PubMed  Google Scholar 

  • Jiménez M, Chazarra S, Escribano J, Cabanes J, Garcia-Carmona F (2001) Competitive inhibition of mushroom tyrosinase by 4-substituted benzaldehydes. J Agric Food Chem 49:4060–4063

    Article  PubMed  Google Scholar 

  • Kobashi K, Takebe S, Terashima N (1975) Inhibition of urease activity by hydroxamic acid derivatives of amino acids. J Biochem 77:837–843

    CAS  PubMed  Google Scholar 

  • Lau SS, Monks TJ, Everitt JI, Kleymenova E, Walker CL (2001) Carcinogenicity of a nephrotoxic metabolite of the “nongenotoxic” carcinogen hydroquinone. Chem Res Toxicol 14:25–33

    Article  CAS  PubMed  Google Scholar 

  • Lin YS, Chen SH, Huang WJ, Chen CH, Chien MY, Lin SY, Hou WC (2012a) Effects of nicotinic acid derivatives on tyrosinase inhibitory and antioxidant activities. Food Chem 132:2074–2080

    Article  CAS  Google Scholar 

  • Lin YS, Chuang MT, Chen CH, Chien MY, Hou WC (2012b) Nicotinic acid hydroxamate downregulated the melanin synthesis and tyrosinase activity through activating the MEK/ERK and AKT/GSK3β signaling pathways. J Agric Food Chem 60:4859–4864

    Article  CAS  PubMed  Google Scholar 

  • Liu DZ, Lin YS, Hou WC (2004) Monohydroxamates of aspartic acid and glutamic acid exhibit antioxidant and angiotensin converting enzyme inhibitory activities. J Agric Food Chem 52:2386–2390

    Article  CAS  PubMed  Google Scholar 

  • Liu YH, Wu WC, Lu YL, Lai YJ, Hou WC (2010) Antioxidant and amine oxidase inhibitory activities of hydroxyurea. Biosci Biotechnol Biochem 74:1256–1260

    Article  CAS  PubMed  Google Scholar 

  • McMahon AM, Doyle EM, Brooks S, O’Connor KE (2007) Biochemical characterisation of the coexisting tyrosinase and laccase in the soil bacterium Pseudomonas putida F6. Enzyme Microb Tech 40:1435–1441

    Article  CAS  Google Scholar 

  • Muri E, Nieto M, Sindelar R, Williamson J (2002) Hydroxamic acids as pharmacological agents. Curr Med Chem 9:1631–1653

    Article  CAS  PubMed  Google Scholar 

  • Neilands JB (1967) Hydroxamic acids in nature. Science 156:1443–1447

    Article  CAS  PubMed  Google Scholar 

  • Schurink M, van Berkel WJ, Wichers HJ, Boeriu CG (2007) Novel peptides with tyrosinase inhibitory activity. Peptides 28:485–495

    Article  CAS  PubMed  Google Scholar 

  • Seo S-Y, Sharma VK, Sharma N (2003) Mushroom tyrosinase: recent prospects. J Agric Food Chem 51:2837–2853

    Article  CAS  PubMed  Google Scholar 

  • Tegoni M, Remelli M (2012) Metallacrowns of copper (II) and aminohydroxamates: thermodynamics of self assembly and host-guest equilibria. Coord Chem Rev 256:289–315

    Article  CAS  Google Scholar 

  • Tomita K, Fukuda M, Kawasaki K (1990) Mechanism of arbutin inhibitory effect on melanogenesis and effect on the human skin with cosmetic used. Fragrance J 6:72–77

    Google Scholar 

  • Ubeid AA, Zhao L, Wang Y, Hantash BM (2009) Short-sequence oligopeptides with inhibitory activity against mushroom and human tyrosinase. J Invest Dermatol 129:2242–2249

    Article  PubMed  Google Scholar 

  • Wang GJ, Lin SY, Wu WC, Hou WC (2007) DPPH radical scavenging and semicarbazide-sensitive amine oxidase inhibitory and cytotoxic activities of Taiwanofungus camphoratus (Chang-Chih). Biosci Biotechnol Biochem 71:1873–1878

    Article  CAS  PubMed  Google Scholar 

  • Yasumoto K, Yokoyama K, Takahashi K, Tomita Y, Shibahara S (1997) Functional analysis of microphthalmia-associated transcription factor in pigment cell-specific transcription of the human tyrosinase family genes. J Biol Chem 272:503–509

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to express thanks to National Science Council, Republic of China (NSC 96-2313-B-038 -001 -MY3, NSC 99-2313-B-038-001-MY2) for financial supports.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan

    Yin-Shiou Lin & Wen-Chung Wu

  2. Department of Primary Care Medicine, Taipei Medical University Hospital, Taipei, Taiwan

    Shyr-Yi Lin

  3. Department of General Medicine, School of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei, Taiwan

    Shyr-Yi Lin

  4. Graduate Institute of Pharmacognosy, Taipei Medical University and Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, 250 Wu-Hsing Street, Taipei, Taiwan

    Wen-Chi Hou

Authors
  1. Yin-Shiou Lin
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  2. Wen-Chung Wu
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  3. Shyr-Yi Lin
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  4. Wen-Chi Hou
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Corresponding authors

Correspondence to Shyr-Yi Lin or Wen-Chi Hou.

Additional information

Y.-S. Lin and W.-C. Wu contributed equally to this study.

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Lin, YS., Wu, WC., Lin, SY. et al. Glycine hydroxamate inhibits tyrosinase activity and melanin contents through downregulating cAMP/PKA signaling pathways. Amino Acids 47, 617–625 (2015). https://doi.org/10.1007/s00726-014-1895-8

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  • DOI: https://doi.org/10.1007/s00726-014-1895-8

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