APP17肽通过抑制细胞内ROS保护紫外线照射后人皮肤成纤维细胞

Objective Ultraviolet light (UV) is known to cause photoaging of skin.UV irradiation can damage proliferation capacity and induce collagenase in fibroblasts in the dermis .Many researchers have explored the potential photo-protective agents;however,no ideal agent has been widely accepted .Amyloid precursor protein 17-mer peptide (APP17-mer peptide),an active peptide segment,has been reported to be responsible for the trophic effect in clonal CNS neuronal line ,fibroblast cell line and HaCat cells.The aim of this study was to explore the effects of APP17-mer peptide on cultured fibroblasts after ultraviolet irradiation .Methods Human skin fibroblasts were cultured in DMEM medium with or without APP 17-mer peptide (concentrations ranging from 20 μmol/L,40 μmol/L,to 80 μmol/L).The cultured fibroblasts were exposed to a single UV irradiation,and the proliferation activity of fibroblasts was detected by a MTT assay .The ex-pression of matrix metalloproteinase-1 (MMP-1) mRNA was analyzed quantitatively following real -time RT-PCR.The generation of intracellular reactive oxygen species (ROS) was measured with fluorescent quantita-tion method.Results A single exposure to UV irradiation depressed proliferation activity of fibroblasts com -pared with sham-irradiated control (P ＜0.05).40 μmol/L and 80 μmol/L APP17-mer peptide increased the cellular proliferation activity in UV irradiated and unirradiated fibroblasts (P ＜0.05),however,20 μmol/L did not show such protective effects (P ＞0.05).A single exposure of fibroblasts to UV irradiation resulted in 1.78 fold up-regulation of MMP-1 mRNA compared with unirradiated sample (P ＜0.05),and 40 μmol/L and 80 μmol/L APP17-mer peptide decreased the expression of MMP -1 mRNA (P ＜0.05 and P ＜0.01,re-spectively).UV irradiation increased generation of ROS in cultured fibroblasts (P ＜0.05).40 μmol/L APP17-mer peptide inhibited the generation of ROS in irradiated fibroblasts .Conclusions APP17-mer pep-tide can enhance proliferation activity of fibroblasts after exposure to UV irradiation ;it can also inhibit MMP-1 mRNA expression and ROS generation induced by UV irradiation .Inhibition of ROS generation after UV irradiation might be involved in the protective mechanism of APP 17 peptide on proliferation activity and collagenase induction in UV-irradiated fibroblasts.