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6-Benzylaminopurine stimulates melanogenesis via cAMP-independent activation of protein kinase A

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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.

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Acknowledgments

This research was partially supported by a grant from the Korean Ministry of Knowledge and Economy through the Program for the Regional Innovation System (B0009310) and the Ministry of Education, Science Technology (MEST) and Korean Industrial Technology Foundation (KOTEF) through the Human Resource Training Project for Regional Innovation.

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Correspondence to Deokhoon Park.

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S. Kim and J. Lee contributed equally to this work.

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Kim, S., Lee, J., Jung, E. et al. 6-Benzylaminopurine stimulates melanogenesis via cAMP-independent activation of protein kinase A. Arch Dermatol Res 301, 253–258 (2009). https://doi.org/10.1007/s00403-008-0924-4

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  • DOI: https://doi.org/10.1007/s00403-008-0924-4

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