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/cm2 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.