Evaluation of human tyrosinase-mediated metabolic activation of leukoderma-inducing phenols
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- NISHIMAKI-MOGAMI Tomoko
- National Institute of Health Sciences
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- ITO Shosuke
- Fujita Health Univ.
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- CUI Hongyan
- National Institute of Health Sciences
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- AKIYAMA Takumi
- National Institute of Health Sciences
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- TAMEHIRO Norimasa
- National Institute of Health Sciences
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- ADACHI Reiko
- National Institute of Health Sciences
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- SHIBATA Norihito
- National Institute of Health Sciences
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- WAKAMATSU Kazumasa
- Fujita Health Univ.
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- IKARASHI Yoshiaki
- National Institute of Health Sciences
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- KONDO Kazunari
- National Institute of Health Sciences
Bibliographic Information
- Other Title
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- 白斑誘発性フェノール類のヒトチロシナーゼによる代謝活性化の評価
Abstract
<p>Chemical leukoderma is a skin depigmentation disorder induced through contact with chemicals, such as monobenzone, rhododendrol, and raspberry ketone. These chemicals are structurally similar to the melanin precursor tyrosine, and oxidized by tyrosinase to highly reactive o-quinone metabolites. This metabolic activation is a critical step in inducing leukoderma through the production of melanocyte-specific damage and immunological responses. In this study, we investigated the effective method to evaluate this step. </p><p>Human tyrosinase-expressing 293T cells were exposed to various phenolic compounds. All 7 leukoderma-inducing phenols were oxidized to o-quinone metabolites and were detected as adducts of cellular glutathione and cysteine, leading to cellular glutathione reduction, whereas 2-S-cysteaminylphenol and 4-n-butylresorcinol were not. In vitro analysis using a soluble truncated human tyrosinase exhibited a similar substrate specificity. In contrast,only 4 leukoderma-inducing phenols showed tyrosinase-dependent cytotoxicity in B16BL6 melanoma cells, in which the cytotoxicity induced by these compounds was effectively blunted by siRNA knockdown of tyrosinase. </p><p>In conclusion, we developed metabolite analytical method to detect metabolic activation of phenolic compounds by analyzing the thiol-adducts of o-quinone metabolites. The cell-based metabolite analysis was superior in sensitivity and specificity compared to cytotoxicity assays for detecting known leukoderma-inducing phenols.1) </p><p>1) Nishimaki-Mogami T, Ito S, et al., J Dermatol Sci. 2022;108:77-86.</p>
Journal
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- Annual Meeting of the Japanese Society of Toxicology
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Annual Meeting of the Japanese Society of Toxicology 50.1 (0), P2-176-, 2023
The Japanese Society of Toxicology
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Details 詳細情報について
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- CRID
- 1390017920607971712
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- Text Lang
- ja
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- Data Source
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- JaLC
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- Abstract License Flag
- Disallowed