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Activation of melanogenesis by vacuolar type H(+)-ATPase inhibitors in amelanotic, tyrosinase positive human and mouse melanoma cells.

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Animals, Vacuolar Proton-Translocating ATPases, Tumor Cells, Cultured, Time Factors, Reverse Transcriptase Polymerase Chain Reaction, metabolism, genetics, RNA, Messenger, antagonists & inhibitors, Proton-Translocating ATPases, Protein Processing, Post-Translational, Monophenol Monooxygenase, Mice, drug effects, Melanosomes, pathology, enzymology, Melanoma, biosynthesis, Melanins, Macrolides, Hydrogen-Ion Concentration, Humans, pharmacology, Enzyme Inhibitors, Enzyme Activation, Dose-Response Relationship, Drug, Cycloheximide, Anti-Bacterial Agents

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      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.

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      10922469

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