Melatonin attenuates the detrimental effects of UVA irradiation in human dermal fibroblasts by suppressing oxidative damage and MAPK/AP‐1 signal pathway in vitro

• Published in: Photodermatology, photoimmunology & photomedicine Vol. 35; no. 4; pp. 221 - 231
• Main Authors: Koçtürk, Semra, Yüksel Egrilmez, Mehtap, Aktan, Şebnem, Oktay, Gülgün, Resmi, Halil, Şimşek Keskin, Hatice, Sert Serdar, Belgin, Erkmen, Tugba, Güner Akdogan, Gül, Özkan, Şebnem
• Format: Journal Article
• Language: English
• Published: England 01-07-2019
• Subjects: activator protein‐1; Adult; Cells, Cultured; Dermis - metabolism; Dermis - pathology; Female; Fibroblasts - metabolism; Fibroblasts - pathology; Humans; Male; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - radiation effects; melatonin; Melatonin - pharmacology; mitogen‐activated protein kinases; Oxidation-Reduction - drug effects; Oxidation-Reduction - radiation effects; oxidative damage; Sunscreening Agents - pharmacology; Transcription Factor AP-1 - metabolism; Ultraviolet Rays - adverse effects; UVA; UVA; oxidative damage; melatonin; activator protein-1; mitogen-activated protein kinases
• ISSN: 0905-4383; 1600-0781
• DOI: 10.1111/phpp.12456

Summary
Background
People living in Mediterranean countries are mostly exposed to solar ultraviolet (UV) radiation that damages skin and results in photoaging which involves activation of epidermal growth factor receptor (EGFR) and downstream signal transduction through mitogen‐activated protein kinases (MAPKs) in fibroblasts. Generation of reactive oxygen/nitrogen species by UV radiation is also critical for EGFR and MAPKs activation. MAPKs are responsible for activation of AP‐1 subunits in the nucleus which induce matrix metalloproteinases. Melatonin, along with its metabolites, are known to be the most effective free radical scavenger and protective agent due to its ability to react with various radicals, lipophilic/hydrophilic structures.
Objectives
In this study, we investigated the effects of melatonin on UVA‐irradiated primary human dermal fibroblasts (HDFs) by following the alteration of molecules from cell membrane to the nucleus and oxidative/nitrosative damage status of the cells in a time‐dependent manner which have not been clearly elucidated yet.
Methods
To mimic UVA dosage in Mediterranean countries, HDFs were exposed to UVA with sub‐cytotoxic dosage (20 J/cm2) after pretreatment with melatonin (1 μmol/L) for 1 hour. Changes in the activation of the molecules and oxidative/nitrosative stress damage were analyzed at different time points.
Results
Our results clearly show that melatonin decreases UVA‐induced oxidative/nitrosative stress damage in HDFs. It also suppresses phosphorylation of EGFR, activation of MAPK/AP‐1 signal transduction pathway and production of matrix metalloproteinases in a time‐dependent manner.
Conclusion
Melatonin can be used as a protective agent for skin damage against intracellular detrimental effects of relatively high dosage of UVA irradiation.