Induction of ATP synthase β by H2O2 induces melanogenesis by activating PAH and cAMP/CREB/MITF signaling in melanoma cells

• Published in: The international journal of biochemistry & cell biology 2013-07, Vol.45 (7), p.1217-1222
• Main Authors: Kim, Hye-Eun, Lee, Seong-Gene
• Format: Article
• Language: English
• Subjects: adenosine triphosphate; Adenosine Triphosphate - metabolism; Adenylyl Cyclase Inhibitors; Animals; apoptosis; Apoptosis - drug effects; ATP; ATP synthase β; binding proteins; cAMP; Cell Line, Tumor; CREB; cyclic AMP; Cyclic AMP - metabolism; Cyclic AMP Response Element-Binding Protein - metabolism; genes; H+/K+-exchanging ATPase; H-transporting ATP synthase; Humans; Hydrogen Peroxide; Imines; melanin; Melanins - biosynthesis; melanocytes; Melanocytes - metabolism; Melanogenesis; melanoma; Melanoma - metabolism; Mice; Microphthalmia-Associated Transcription Factor - metabolism; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondrial Proton-Translocating ATPases - antagonists & inhibitors; Mitochondrial Proton-Translocating ATPases - metabolism; oligomycin; Oligomycins; Oxidative Stress; phenylalanine 4-monooxygenase; Phenylalanine Hydroxylase - metabolism; phosphorylation; polycyclic aromatic hydrocarbons; Signal Transduction - drug effects; transcription factors
• ISSN: 1357-2725; 1878-5875
• DOI: 10.1016/j.biocel.2013.03.006

Hydrogen peroxide (H2O2) production due to oxidative stress is associated with apoptosis and melanogenesis in melanocytes. Here, we analyzed the effects of H2O2 on melanogenesis by measuring the melanin content and analyzing the expression of melanogenesis-related proteins, including cAMP-responsive element binding protein (CREB), microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), and phenylalanine hydroxylase (PAH). Treatment with 1mM H2O2 increased the cellular melanin content; the expression of PAH, TYR, and MITF; and the phosphorylation of CREB in B16F10 and SK-Mel-2 cells. In addition, H2O2 increased the expression of ATP synthase β (ATP5B), a mitochondrial F1 complex, and increased intracellular ATP levels. Studies using the ATP5B inhibitor oligomycin (OM) showed that the induction of cAMP resulted from an increase in ATP caused by the induction of ATP5B. OM treatment increased H2O2-mediated apoptosis via accelerated ATP depletion and apoptosis-related gene expressions. In summary, H2O2 may induce melanogenesis via the upregulation of PAH and activation of cAMP/p-CREB/MITF signaling by increasing intracellular cAMP levels through the induction of ATP5B.