Browsing by Author "Egrilmez, Mehtap Yuksel"

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Citation - WoS: 14
Citation - Scopus: 14
Melatonin Attenuates the Detrimental Effects of Uva Irradiation in Human Dermal Fibroblasts by Suppressing Oxidative Damage and Mapk/Ap-1 Signal Pathway in Vitro
(Wiley, 2019-03-20) Kocturk, Semra; Egrilmez, Mehtap Yuksel; Aktan, Sebnem; Oktay, Gulgun; Resmi, Halil; Keskin, Hatice Simsek; Serdar, Belgin Sert; Akdoğan, Gül
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/cm(2)) after pretreatment with melatonin (1 mu mol/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.
Citation - WoS: 17
Citation - Scopus: 15
Melatonin Prevents Uvb-Induced Skin Photoaging by Inhibiting Oxidative Damage and Mmp Expression Through Jnk/Ap-1 Signaling Pathway in Human Dermal Fibroblasts
(Mdpi, 2022-06-24) Yuksel Egrilmez, Mehtap; Kocturk, Semra; Aktan, Sebnem; Oktay, Gulgun; Resmi, Halil; Simsek Keskin, Hatice; Akdoğan, Gül; Keskin, Hatice Simsek; Ozkan, Sebnem; Egrilmez, Mehtap Yuksel
Exposure to ultraviolet (UV) irradiation causes damage to the skin and induces photoaging. UV irradiation stimulates production of reactive oxygen/nitrogen species, which results in activation of epidermal growth factor receptor (EGFR) and mitogen-activated protein kinases (MAPK) in fibroblasts. MAPKs are responsible for activation of activator protein-1 (AP-1), which subsequently upregulates expression of matrix metalloproteinases (MMPs). Melatonin is a potent free radical scavenger which is known to have photoprotective effects. The aim of this study is to investigate the underlying molecular mechanisms for the photoprotective effects of melatonin in UVB-irradiated primary human dermal fibroblasts (HDFs) in terms of EGFR activation, oxidative/nitrosative damage, JNK/AP-1 activation, MMP activities, and the levels of tissue inhibitors of metalloproteinase-1 (TIMP-1) and type I procollagen (PIP-C). In this study, HDFs were pretreated with 1 mu M of melatonin and then irradiated with 0.1 J/cm(2) of UVB. Changes in the molecules were analyzed at different time points. Melatonin inhibited UVB-induced oxidative/nitrosative stress damage by reducing malondialdehyde, the ratio of oxidized/reduced glutathione, and nitrotyrosine. Melatonin downregulated UV-induced activation of EGFR and the JNK/AP-1 signaling pathway. UVB-induced activities of MMP-1 and MMP-3 were decreased and levels of TIMP-1 and PIP-C were increased by melatonin. These findings suggest that melatonin can protect against the adverse effects of UVB radiation by inhibiting MMP-1 and MMP-3 activity and increasing TIMP-1 and PIP-C levels, probably through the suppression of oxidative/nitrosative damage, EGFR, and JNK/AP-1 activation in HDFs.