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.
Ancans
J
J
Department of Biomedical Sciences, University of Bradford, BD7 1DP, Bradford, UK.
Thody
A J
AJ
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