Abstract
Melanosomes are lysosome-related organelles with specialized capabilities of melanin synthesis and movement mediated by the Rab27a-Melanophilin-MyosinVa protein complex. In this study, we found that 2-methyl-naphtho[1,2,3-de]quinolin-8-one (MNQO) induced melanosome aggregation around the nucleus in melan-a melanocytes and in melan-a melanocytes/SP-1 keratinocyte co-cultures without inducing toxicity or changing the melanin content. Western blot and real-time PCR analyses showed that MNQO decreased expression of the Rab27a, Melanophilin and MyosinVa proteins and mRNAs, respectively, in melan-a melanocytes. In a reconstituted human epidermis model, treatment with 0.001% MNQO reduced skin pigmentation. Also, MNQO reduced skin pigmentation in brown guinea pigs induced by UVB irradiation. These results indicated that regulation of melanosome transport may serve as a good target for new skin depigmenting agents and MNQO itself could be a candidate.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism
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Animals
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Biological Transport
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Cell Aggregation
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Cell Count
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Cell Nucleus / metabolism
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Coculture Techniques
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Guinea Pigs
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Humans
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MART-1 Antigen / metabolism
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Melanins / biosynthesis
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Melanocytes / metabolism
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Melanocytes / radiation effects
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Melanosomes / metabolism*
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Melanosomes / radiation effects
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Mice, Inbred C57BL
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Models, Biological
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Myosin Type V / genetics
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Myosin Type V / metabolism
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Naphthalenes / chemistry
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Naphthalenes / metabolism*
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Quinolines / chemistry
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Quinolines / metabolism*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Skin Pigmentation* / radiation effects
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Ultraviolet Rays
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rab27 GTP-Binding Proteins / genetics
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rab27 GTP-Binding Proteins / metabolism
Substances
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2-methyl-naphtho(1,2,3-de)quinolin-8-one
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Adaptor Proteins, Signal Transducing
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MART-1 Antigen
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MLPH protein, human
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Melanins
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Naphthalenes
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Quinolines
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RNA, Messenger
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rab27 GTP-Binding Proteins
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Myosin Type V