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Ascorbic acid increases the activity and synthesis of tyrosinase in B16F10 cells through activation of p38 mitogen-activated protein kinase

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Abstract

Ascorbic acid, a potential antioxidant, is known to inhibit melanogenesis. However, there are conflicting findings that ascorbic acid has very low stability and acts as a pro-oxidant, eventually increasing proliferation and melanin content in melanoma cells. In the present study, we explored the effects of ascorbic acid on the activity and expression of tyrosinase and melanin pigmentation in the presence and absence of α-melanocyte-stimulating hormone (α-MSH) using B16F10 melanoma cells. The mechanism by which ascorbic acid stimulated the expression of tyrosinase was also investigated. No inhibitory effect on melanin content was observed in ascorbic acid-treated cells, regardless of the presence of α-MSH. Ascorbic acid stimulated the activity and expression of tyrosinase and increased the expression of melanogenic regulatory factors, such as tyrosinase-related protein-1 (TRP-1), dihydroxyphenylalaminechrome tautomerase (TRP-2), and microphthalmia-associated transcription factor (MITF). Ascorbic acid also induced phosphorylation of p38 mitogen-activated protein kinase (MAPK). The inhibition of p38 MAPK pathway by SB203580 led to the suppression of tyrosinase, TRP-1, and TRP-2 expression in cells treated with ascorbic acid. Combined treatment with N-acetyl-l-cysteine and/or desferrioxamine mesylate attenuated the stimulating effect of ascorbic acid on tyrosinase activation in the cells. Collectively, ascorbic acid stimulates tyrosinase activity and expression in B16F10 cells via activation of p38 MAPK signaling and subsequent up-regulation of MITF, tyrosinase, and TRP expression.

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Acknowledgments

This work was supported by a grant from the RDA, Ministry of Agriculture and Forestry, Republic of Korea.

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Authors and Affiliations

  1. Research Center of Bioactive Materials, Chonbuk National University, Jeonju, 561-756, South Korea

    Seung-Ah Lee & Jeong-Chae Lee

  2. Department of Nursing, Chonnam Techno College, Chonnam, 516-911, South Korea

    Seung-Ah Lee

  3. Graduate Center for Toxicology, University of Kentucky, Lexington, KY, 40536-0001, USA

    Young-Ok Son

  4. School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA

    Sung-Ho Kook

  5. National Livestock Research Institute, RDA, Suweon, 441-706, South Korea

    Ki-Choon Choi

  6. Institute of Oral Biosciences and BK21 Program, Chonbuk National University, Jeonju, 561-756, South Korea

    Jeong-Chae Lee

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  1. Seung-Ah Lee
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Correspondence to Jeong-Chae Lee.

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S.-A. Lee and Y.-O. Son contributed equally to this work.

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Lee, SA., Son, YO., Kook, SH. et al. Ascorbic acid increases the activity and synthesis of tyrosinase in B16F10 cells through activation of p38 mitogen-activated protein kinase. Arch Dermatol Res 303, 669–678 (2011). https://doi.org/10.1007/s00403-011-1158-4

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  • DOI: https://doi.org/10.1007/s00403-011-1158-4

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