title: Antimelanogenic effect of c-phycocyanin through modulation of tyrosinase expression by upregulation of ERK and downregulation of p38 MAPK signaling pathways.
abstract: BACKGROUND
  Pigmentation is one of the essential defense mechanisms against oxidative stress or UV irradiation; however, abnormal hyperpigmentation in human skin may pose a serious aesthetic problem. C-phycocyanin (Cpc) is a phycobiliprotein from spirulina and functions as an antioxidant and a light harvesting protein. Though it is known that spirulina has been used to reduce hyperpigmentation, little literature addresses the antimelanogenic mechanism of Cpc. Herein, we investigated the rationale for the Cpc-induced inhibitory mechanism on melanin synthesis in B16F10 melanoma cells.
  
  
  METHODS
  Cpc-induced inhibitory effects on melanin synthesis and tyrosinase expression were evaluated. The activity of MAPK pathways-associated molecules such as MAPK/ERK and p38 MAPK, were also examined to explore Cpc-induced antimelanogenic mechanisms. Additionally, the intracellular localization of Cpc was investigated by confocal microscopic analysis to observe the migration of Cpc.
  
  
  RESULTS
  Cpc significantly (P < 0.05) reduced both tyrosinase activity and melanin production in a dose-dependent manner. This phycobiliprotein elevated the abundance of intracellular cAMP leading to the promotion of downstream ERK1/2 phosphorylation and the subsequent MITF (the transcription factor of tyrosinase) degradation. Further, Cpc also suppressed the activation of p38 causing the consequent disturbed activation of CREB (the transcription factor of MITF). As a result, Cpc negatively regulated tyrosinase gene expression resulting in the suppression of melanin synthesis. Moreover, the entry of Cpc into B16F10 cells was revealed by confocal immunofluorescence localization and immunoblot analysis.
  
  
  CONCLUSIONS
  Cpc exerted dual antimelanogenic mechanisms by upregulation of MAPK/ERK-dependent degradation of MITF and downregulation of p38 MAPK-regulated CREB activation to modulate melanin formation. Cpc may have potential applications in biomedicine, food, and cosmetic industries.
authors: Department of Applied Chemistry, National Chi Nan University, Puli, Nantou, 545, Taiwan. lw25@ncnu.edu.tw
authors: Li-Chen
authors: LC
authors: Wu
authors: Yu-Yun
authors: YY
authors: Lin
authors: Szu-Yen
authors: SY
authors: Yang
authors: Yu-Ting
authors: YT
authors: Weng
authors: Yi-Ting
authors: YT
authors: Tsai
mesh_terms: D004789:Enzyme Activation; D005786:Gene Expression Regulation; D006801:Humans; D017495:Hyperpigmentation / Q000517:prevention & control; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000235:genetics; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008546:Melanoma, Experimental / Q000201:enzymology; D051739:Microphthalmia-Associated Transcription Factor / Q000187:drug effects; D014442:Monophenol Monooxygenase / Q000096:biosynthesis*; D010766:Phosphorylation; D010798:Phycocyanin / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D053545:Spirulina / Q000378:metabolism; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
chemical_list: D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D014157:Transcription Factors; D010798:Phycocyanin; D014442:Monophenol Monooxygenase; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases