title: Disulfanyl peptide decreases melanin synthesis via receptor-mediated ERK activation and the subsequent downregulation of MITF and tyrosinase.
abstract: OBJECTIVE
  Bioactive peptides are commonly used in cosmeceutical purpose. This study was performed to search for an effective and short hypopigmenting peptide using normal human melanocytes as a screening model. A peptide that exhibits multitarget activities will be a promising peptide.
  
  
  METHODS
  Depigmenting effects were tested in normal human melanocytes. One peptide was selected, and signalling mechanism was investigated by Western blotting and immunofluorescent microscopic examination.
  
  
  RESULTS
  A novel hypopigmenting peptide (dSHP) has been found to inhibit the production of melanin. This peptide significantly decreases tyrosinase activity but was not effective in a direct in vitro assay. It also induces the prolonged activation of ERK, and subsequently downregulates the levels of MITF. PD98059 abolished the dSHP-induced downregulation of MITF. These findings indicate that the dSHP-induced activation of ERK contributes to a reduced melanin synthesis via the downregulation of MITF. Fluorescent microscopic studies were consistent with such findings. Pertussis toxin reverses the downregulation of MITF, which means that the receptor-mediated ERK activation is involved. Moreover, it was also found that downregulation of MITF was clearly inhibited by lysosomal inhibitor (chloroquine).
  
  
  CONCLUSIONS
  Novel tetrapeptide dSHP reduces the melanin synthesis by a receptor-mediated pathway. Furthermore, dSHP works by ERK activation and key transcription factor MITF degradation. Thus, it may be a good candidate as an effective hypopigmenting cosmetic agent.
authors.affiliation: Department of Dermatology, Seoul National University Bundang Hospital, 82 Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Korea.
authors.forename: H-R
authors.initials: HR
authors.lastname: Choi
authors.affiliation: Department of Dermatology, Seoul National University Bundang Hospital, 82 Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Korea.
authors.forename: Y-A
authors.initials: YA
authors.lastname: Kang
authors.affiliation: Department of Dermatology, Seoul National University Bundang Hospital, 82 Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Korea.
authors.forename: H-S
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Dermatology, Seoul National University Bundang Hospital, 82 Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Korea.
authors.forename: K-C
authors.initials: KC
authors.lastname: Park
mesh_terms: D015536:Down-Regulation / Q000187:drug effects*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism*; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*
chemical_list: C497234:MITF protein, human; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D010455:Peptides; D014442:Monophenol Monooxygenase; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: ERK; MITF; Peptide; melanogenesis