title: Photoprotective effect of the N-terminal 5-mer peptide analog P165 of amyloid precursor protein in human dermal fibroblasts.
abstract: BACKGROUND
  We showed in our previous study that the N-terminal 17-mer peptide of amyloid precursor protein (APP17-mer peptide), an active peptide segment with trophic and antioxidative effects, protects skin fibroblasts against ultraviolet (UV) damage and downregulates matrix metalloproteinase 1 (MMP-1) expression. The aim of the current study was to explore the protective effects of P165, the N-terminal 5-mer peptide analog of amyloid precursor protein that is resistant to enzymolysis, on UVA-induced damage in human dermal fibroblasts (HDFs).
  
  
  METHODS
  HDFs were cultured in Dulbecco's modified Eagle's medium without and with P165 (concentrations were 1, 10, and 100 µmol/L). Then, 15 J/cm(2) UVA irradiation was used to obtain the UV-irradiated model. Cell proliferation was analyzed using MTT kit. The collagen type I and MMP-1 contents in cell lysate were determined by enzyme-linked immunosorbent assay (ELISA). Fluorometric assays were performed to detect the formation of intracellular reactive oxygen species (ROS) in the cells.
  
  
  RESULTS
  P165 significantly protected the HDFs against UVA-induced cytotoxicity. Compared with the UVA-irradiated control, 1, 10, and 100 µmol/L P165 elevated cell proliferation by 14.98% (P < 0.05), 17.52% (P < 0.01) and 28.34% (P < 0.001), respectively. Simultaneously, 10 and 100 µmol/L P165 increased collagen type I content (both P < 0.05). Moreover, P165 treatment (all concentrations) also markedly suppressed the UVA-induced MMP-1 expression (all P < 0.001). P165 at 1, 10, and 100 µmol/L also reduced UVA-induced ROS generation by 11.27%, 13.69% (both P < 0.05), and 25.48% (P < 0.001), respectively.
  
  
  CONCLUSIONS
  P165 could protect the HDFs against UVA-induced photodamage, including cytotoxicity, and MMP-1 generation. Furthermore, it also increased the collagen type I content in the cells. The inhibitory effect on intracellular ROS generation might be involved in these photoprotective effects. Thus, P165 may be a useful candidate in the prevention and treatment of skin photoaging.
authors.affiliation: Department of Dermatology and Venereology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Dermatology and Venereology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Dermatology and Venereology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Yuying
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Pharmacology, Xuanwu Hospital, Capital Medical University; Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Central Laboratory, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Dermatology and Venereology, Capital Medical University, Beijing 100069, China. Email: drlianshi@sina.com.
authors.forename: Shi
authors.initials: S
authors.lastname: Lian
authors.affiliation: Department of Dermatology and Venereology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China. Email: zhuwei@xwh.ccmu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000494:pharmacology*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D012867:Skin / Q000166:cytology*; D014466:Ultraviolet Rays
chemical_list: D016564:Amyloid beta-Protein Precursor