Abstract
In this study, we describe the activation of melanogenesis by selective vacuolar type H(+)-ATPase inhibitors (bafilomycin A1 and concanamycin A) in amelanotic human and mouse melanoma cells which express tyrosinase but show no melanogenesis. Addition of the inhibitors activated tyrosinase within 4 h, and by 24 h the cells contained measurable amounts of melanin. These effects were not inhibited by cycloheximide (2 microgram/ml) which is consistent with a post-translational mechanism of activation. Our findings suggest that melanosomal pH could be an important and dynamic factor in the control of melanogenesis in mammalian cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Bacterial Agents / pharmacology
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Cycloheximide / pharmacology
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Dose-Response Relationship, Drug
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Enzyme Activation / drug effects
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Enzyme Inhibitors / pharmacology*
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Humans
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Hydrogen-Ion Concentration
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Macrolides*
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Melanins / biosynthesis*
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Melanins / metabolism
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Melanoma / enzymology*
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Melanoma / metabolism
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Melanoma / pathology
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Melanosomes / drug effects*
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Melanosomes / metabolism
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Mice
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Monophenol Monooxygenase / genetics
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Monophenol Monooxygenase / metabolism*
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Protein Processing, Post-Translational
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Proton-Translocating ATPases / antagonists & inhibitors*
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Proton-Translocating ATPases / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Time Factors
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Tumor Cells, Cultured
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Vacuolar Proton-Translocating ATPases*
Substances
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Anti-Bacterial Agents
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Enzyme Inhibitors
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Macrolides
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Melanins
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RNA, Messenger
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concanamycin A
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bafilomycin A1
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Cycloheximide
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Monophenol Monooxygenase
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Vacuolar Proton-Translocating ATPases
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Proton-Translocating ATPases