ArgTX-636, a polyamine isolated from spider venom: A novel class of melanogenesis inhibitors |
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| Institution: | 1. Aix Marseille Univ, CNRS, ICR UMR 7273, 13397 Marseille, Cedex 20, France;2. Laboratoire In’Oya SAS—Pôle d’Activités Yvon Morandat, 1480 Av. d’Arménie, 13120 Gardanne, France;3. Aix Marseille Univ, INSERM, UMR 911, CRO2, 13385 Marseille, Cedex 5, France;4. Laboratoire LATOXAN SAS, 845 avenue Pierre Brossolette, 26800 Portes lès Valence, France;1. Department of Anatomy, Physiology, and Genetics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA;2. Department of Psychiatry, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA;3. Program in Neuroscience, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA;4. Neurotoxicology Branch, United States Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010, USA;1. Istituto di Biochimica delle Proteine – CNR, Via P. Castellino 111, 80131 Napoli, Italy;2. Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy;3. Department of Chemistry, College of Science, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia;4. Università degli Studi di Firenze, Polo Scientifico, Dipartimento NEIROFABA;Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Firenze), Italy;1. Yokohama City University, Seto 22-2, Kanazawa-ku, Yokohama 236-0027, Japan;2. Faculty of Fisheries Sciences, Hokkaido University, Hakodate 041-8611, Japan;1. Division of Biotechnology and State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, CAS, Dalian 116023, China;2. Department of Chemistry, Liaoning Key Laboratory for the Synthesis and Application of Functional Compounds, Bohai University, Jinzhou 121013, China;1. Division of Microbiology, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829, Japan;2. Division of Biophysics, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829, Japan;3. Division of Microbiology and Infectious Diseases, Department of Pathology, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga 520-2192, Japan;1. Structural Biology Laboratory, Department of Chemistry, University of York, York YO10 5DD, United Kingdom;2. Dept. of Organic Chemistry, Faculty of Chemistry, University of Seville, Prof. García González 1, E-41012 Seville, Spain |
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| Abstract: | To discover new molecules with an inhibitory activity of melanogenesis a hundred of scorpions, snakes, spiders and amphibians venoms were screened for their capacity to inhibit mushroom tyrosinase using 3,4-l-dihydroxyphenylalanine (l-DOPA) as substrate.The Argiope lobata spider venom proved to be the most active. HPLC fraction containing Argiotoxine-636 (ArgTX-636), a polyamine known for its numerous biological activities, was found to also show a good regulation activity of melanogenesis by inhibiting DOPA and 5,6-dihydroxyindole-2-carboxylic acid (DHICA) oxidases activities, wore by tyrosinase (TYR) and tyrosinase-related protein 1 (TRP-1), respectively. Our results demonstrate that ArgTX-636 reduced the mushroom tyrosinase activity in a dose-dependent way with a maximal half inhibitory concentration (IC50) value of 8.34 μM, when l-DOPA is used as substrate. The Lineweaver–Burk study showed that ArgTX-636 is a mixed type inhibitor of the diphenolase activity. Moreover, ArgTX-636 inhibits DHICA oxydase activity of mushroom tyrosinase activity with IC50 at 41.3 μM. ArgTX-636 has no cytotoxicity in B16F10 melanoma cells at concentrations up to 42.1 μM. The effect of ArgTX-636 on melanogenesis showed that melanin production in B16F10 melanoma cell decreased by approximatively 70% compared to untreated cells. ArgTX-636 displayed no significant effect on the TYR expression while the protein level of TRP-1 decreased in B16F10 cells. Thus, ArgTX-636 could have particular interest for cosmetic and/or pharmaceutical use in order to reduce important dermatoses in black and mixed skins. |
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| Keywords: | Melanogenesis Tyrosinase Tyrosinase related protein 1 (TRP-1) Hyperpigmentation DOPA oxydase activity DHICA oxydase activity Spider venoms Argiotoxine"} {"#name":"keyword" "$":{"id":"k0045"} "$$":[{"#name":"text" "_":"ArgTX-636 |
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