Activation of melanogenesis by vacuolar type H(+)-ATPase inhibitors in amelanotic, tyrosinase positive human and mouse melanoma cells.
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.
Department of Biomedical Sciences, University of Bradford, BD7 1DP, Bradford, UK.
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D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018942:Macrolides; D008543:Melanins / Q000096:biosynthesis* / Q000378:metabolism; D008545:Melanoma / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D020460:Melanosomes / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014407:Tumor Cells, Cultured; D025262:Vacuolar Proton-Translocating ATPases
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D018942:Macrolides; D008543:Melanins; D012333:RNA, Messenger; C036978:concanamycin A; C040929:bafilomycin A1; D003513:Cycloheximide; D014442:Monophenol Monooxygenase; D025262:Vacuolar Proton-Translocating ATPases; D006180:Proton-Translocating ATPases