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

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

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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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