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

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.

Mechanistic Studies of Anti-Hyperpigmentary Compounds: Elucidating Their Inhibitory and Regulatory Actions

“…Although PTU could achieve similar effects with the compounds, its concentration was much higher than the tested compounds. On the other hand, PKA is a critical enzyme responsible for the regulation of numerous cellular pathways within cells [31]. It affects the activity of a number of signaling proteins along the melanogenic pathway.…”

Suppression of α-MSH and IBMX-induced melanogenesis by cordycepin via inhibition of CREB and MITF, and activation of PI3K/Akt and ERK-dependent mechanisms

“…This pathway is apparently regulated by activation of ERK, whose phosphorylation allows the expression of MITF, leading to its degradation. On the other hand, the activation of ERK can result in phosphorylation of cAMP related binding protein (CREB), which binds to the CRE consensus motif in the MITF promoter to up-regulate MITF gene expression (15).…”

Anti-adipogenesis by 6-thioinosine is mediated by downregulation of PPAR γ through JNK-dependent upregulation of iNOS

“…Inosine was recently implicated in cellular responses to ischemia in the brain and skeletal muscle, and it has been reported to activate A 3 receptors [10][11][12][13]. Additionally, 6-benzylaminopurine (6-BAP), which is a purine derivative, has been found to induce melanogenesis in B16 melanoma cells [16]. These various functions of purine and its derivatives led us to evaluate their inhibitory effect on adipogenesis.…”