Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.10.3.1 (tyrosinase)
 9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To develop effective skin-lightening agents, we tested medicinal herbal extracts for their melanogenic-inhibitory activities. We isolated a sesquiterpenoid compound from the extract of Atractylodis Rhizoma Alba using the bioactivity-guided fractionation and identified it as selina-4(14),7(11)-dien-8-one (compound 1) with spectroscopic methods. Compound 1 dramatically reduced melanin synthesis of melan-a cells without any apparent cytotoxicity. Compound 1 did not inhibit cell-free tyrosinase activity but decreased tyrosinase activity in melanocytes. These effects were attributed to reduced expression of melanogenic enzymes such as tyrosinase, tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (TRP-2). These results suggest that compound 1 may be an effective skin-lightening agent that regulates expression of melanogenic enzymes.
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PMID:Inhibition of melanogenesis by selina-4(14),7(11)-dien-8-one isolated from Atractylodis Rhizoma Alba. 1740 9

Monobenzone (hydroquinone monobenzylether, 1) is a potent skin depigmenting agent that causes irreversible loss of epidermal melanocytes by way of a tyrosinase-dependent mechanism so far little understood. Herein, we show that 1 can be oxidized by mushroom tyrosinase to an unstable o-quinone (1-quinone) that has been characterized by comparison of its properties with those of a synthetic sample obtained by o-iodoxybenzoic acid-mediated oxidation of 1. Preparative scale oxidation of 1 with tyrosinase and catalytic l-DOPA, followed by reductive workup and acetylation, led to the isolation of two main products that were identified as the acetylated catechol derivative 4 and an unusual biphenyl-type dimer of 4, acetylated 5, arising evidently by coupling of 4 with 1-quinone. In the presence of l-cysteine or N-acetyl-l-cysteine, formation of 4 and 5 was inhibited, and the reaction led instead to monoadducts (6 or 9) and diadducts (7 and 8). A similar behavior was observed when the tyrosinase-promoted oxidation of 1 was carried out in the presence of sulfhydryl-containing peptides, such as reduced glutathione, or proteins, such as bovine serum albumin (BSA), as inferred by detection of adduct 9 by high pressure liquid chromatography-electrochemical detection (HPLC-ED) after acid hydrolysis. The generation and reaction chemistry of 1-quinone described in this article may bear relevance to the etiopathogenetic mechanisms of monobenzone-induced leukoderma as well as to the recently proposed haptenation hypothesis of vitiligo, a disabling pigmentary disorder characterized by irreversible melanocyte loss.
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PMID:A reactive ortho-quinone generated by tyrosinase-catalyzed oxidation of the skin depigmenting agent monobenzone: self-coupling and thiol-conjugation reactions and possible implications for melanocyte toxicity. 1961 May 92

In this study, we report the previously unknown mechanism of inducing robust anti-melanoma immunity by the vitiligo-inducing compound monobenzone. We show monobenzone to increase melanocyte and melanoma cell immunogenicity by forming quinone-haptens to the tyrosinase protein and by inducing the release of tyrosinase- and melanoma antigen recognized by T cells-1 (MART-1)-containing CD63+ exosomes following melanosome oxidative stress induction. Monobenzone further augments the processing and shedding of melanocyte-differentiation antigens by inducing melanosome autophagy and enhanced tyrosinase ubiquitination, ultimately activating dendritic cells, which induced cytotoxic human melanoma-reactive T cells. These T cells effectively eradicate melanoma in vivo, as we have reported previously. Monobenzone thereby represents a promising and readily applicable compound for immunotherapy in melanoma patients.
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PMID:Skin-depigmenting agent monobenzone induces potent T-cell autoimmunity toward pigmented cells by tyrosinase haptenation and melanosome autophagy. 2156 76

Differential expression of antioxidant enzymes in various growth and differentiation stages has been documented in several plant species. We studied here, the difference in the levels of protein content and antioxidant enzymes activity at two stages of maturity, named young and mature in neem (Azadirachta indica A. Juss), pigeonpea (Cajanus cajan (L.) mill sp) and mulberry (Morus Alba L.) leaves. The results showed that detached neem and pigeonpea mature leaves possessed higher activities of catalase (CAT) and peroxidase (POD) and lower activities of polyphenol oxidase (PPO) and ascorbate peroxidase (APX) as compared with young leaves. However, glutathione reductase (GR) showed higher activity in mature leaves of neem, whereas no change in its activity was observed in pigeonpea. On the other hand, antioxidant enzymes in mulberry showed either positive (PPO) or negative (POD, GR, APX) correlation with the progression of leaf maturity. Apparently the trend of changes in antioxidant enzymes activity during leaf development is species-specific: their activity higher at mature stage in some plants and lower in others.
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PMID:Antioxidant enzyme changes in neem, pigeonpea and mulberry leaves in two stages of maturity. 2289 4

Monobenzone is a 4-substituted phenol that can induce vitiligo and antimelanoma immunity. We investigated the influence of the chemical structure on the biological activity of a series of structurally related 4-substituted phenols. All phenols inhibited cellular melanin synthesis, and eight of ten phenols inhibited tyrosinase activity, using the MBTH assay. These phenols also induced glutathione (GSH) depletion, indicative of quinone formation and protein thiol binding, which can increase the immunogenicity of melanosomal proteins. Specific T-cell activation was found upon stimulation with phenol-exposed pigmented cells, which also reacted with unexposed cells. In contrast, 4-tertbutylphenol induced immune activation was not restricted to pigment cells, analogous to contact sensitization. We conclude that 4-substituted phenols can induce specific T-cell responses against melanocytes and melanoma cells, also acting at distant, unexposed body sites, and may confer a risk of chemical vitiligo. Conversely, these phenols may be applicable to induce specific antimelanoma immunity.
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PMID:Mechanism of action of 4-substituted phenols to induce vitiligo and antimelanoma immunity. 3076 90