6-Benzylaminopurine Stimulates Melanogenesis via cAMP-independent Activation of Protein Kinase A

Arch Dermatol Res. 2009 Mar;301(3):253-8. doi: 10.1007/s00403-008-0924-4. Epub 2009 Jan 3.

Abstract

Melanogenesis is a physiological process that results in the synthesis of melanin pigments, which play a crucial protective role against skin photocarcinogenesis. The present study was designed to determine the effects of 6-benzylaminopurine (6-BAP) on melanogenesis and elucidate the molecular events of melanogenesis induced by 6-BAP. To elucidate the pigmenting effect of 6-BAP and its mechanism, several experiments were performed in B16 melanoma cells. Melanin content, tyrosinase activity, cAMP production, and Western blots for proteins which are involved in melanogenesis were introduced in this study. Melanin content and tyrosinase activity increased in response to treatment with 6-BAP in a concentration-dependent manner. The tyrosinase, TRP-1, TRP-2 and MITF protein levels were found to increase significantly in response to 6-BAP in a time-dependent manner. In addition, Western blot analysis revealed that 6-BAP increased the phosphorylated level of CRE-binding protein. The increased melanin synthesis that was induced by treatment with 6-BAP treatment was reduced significantly in response to co-treatment with H-89 [a protein kinase A (PKA) inhibitor], whereas co-treatment with SB203580 (a p38 MAPK inhibitor) and Ro-32-0432 (a PKC inhibitor) did not attenuate the increase in melanin content levels that was induced by 6-BAP. In a cAMP production assay, 6-BAP did not increase the intracellular cAMP level. These findings suggest that 6-BAP activates PKA via a cAMP-independent pathway and subsequently stimulates melanogenesis by up-regulating MITF and tyrosinase expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzyl Compounds
  • Cell Line, Tumor
  • Cells, Cultured
  • Cyclic AMP / metabolism*
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Dose-Response Relationship, Drug
  • Kinetin / pharmacology*
  • Melanins / metabolism*
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Mice
  • Microphthalmia-Associated Transcription Factor / metabolism
  • Monophenol Monooxygenase / metabolism
  • Plant Growth Regulators / pharmacology*
  • Purines
  • Signal Transduction / physiology
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology
  • Time Factors

Substances

  • Benzyl Compounds
  • Creb1 protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • Melanins
  • Microphthalmia-Associated Transcription Factor
  • Mitf protein, mouse
  • Plant Growth Regulators
  • Purines
  • Cyclic AMP
  • Monophenol Monooxygenase
  • Cyclic AMP-Dependent Protein Kinases
  • benzylaminopurine
  • Kinetin