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

FEBS Lett. 2000 Jul 28;478(1-2):57-60. doi: 10.1016/s0014-5793(00)01795-6.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Macrolides
  • Melanins
  • RNA, Messenger
  • concanamycin A
  • bafilomycin A1
  • Cycloheximide
  • Monophenol Monooxygenase
  • Vacuolar Proton-Translocating ATPases
  • Proton-Translocating ATPases