L‐Ergothioneine scavenges superoxide and singlet oxygen and suppresses TNF‐α and MMP‐1 expression in UV‐irradiated human dermal fibroblasts

Abstract

Ergothioneine (EGT) is a sulfur‐containing amino acid, and is presumed to function as a natural antioxidant. The purpose of this study was to identify the nature of the antioxidant activity and investigate the effects of EGT on UV‐induced cellular response. In chemical studies, EGT scavenged the superoxide anion radical (•O2–) and singlet oxygen (1O2). In cultured fibroblasts, EGT suppressed TNF‐α upregulation by UVB irradiation. In addition, in fibroblasts exposed to UV‐A, EGT suppressed the expression of matrix metalloproteinase 1 (MMP‐1) protein by nearly 50% and reduced MMP‐1 mRNA expression. From these results, we conclude that EGT scavenges reactive oxygen species generated by both type I and type II photosensitization and suppresses both TNF‐α expression and MMP‐1 at their transcriptional level. EGT may reduce skin anti‐aging effects after UV irradiation by the scavenging of •O2– and 1O2, and reducing signals for protease and inflammatory activity.

Dermato-protective properties of ergothioneine through induction of Nrf2/ARE-mediated antioxidant genes in UVA-irradiated Human keratinocytes

“…In our study, elevated ROS in UVA exposed cells were substantially inhibited by EGT pretreatment, indicating the free radical scavenging activity and dermato-protective properties of EGT at low concentrations. Under different stress conditions, in vitro studies have shown that EGT is capable of scavenging the various free radicals, such as superoxide, hydroxyl and peroxynitrite [16,22,28], and deactivate the 1 O 2 at a higher rate than GSH [29]. Although in vivo antioxidant properties of EGT not fully established, the accumulation, distribution and scavenging properties of EGT emphasizes its antioxidant property.…”

“…Furthermore, EGT treatment reported to scavenge the 1 O 2 radicals, and suppress the expression of matrix metalloproteinase-1 in UVA-irradiated dermal fibroblasts [22].…”

“…But, these findings are not consistent with previous studies, who reported the cytoprotective properties of EGT at higher concentrations (20 µM -0.5 mM). This discrepancy may be due to the differences in incubation period and/or cell type used in the study[21,22]. Indeed, the proliferation of HaCaT cells was significantly increased by 500 nM EGT, which indicates EGT could induce keratinocyte proliferation in vitro.…”

Uptake and Protective Effects of Ergothioneine in Human Endothelial Cells

“…Ergothioneine was first identified as an antioxidant in cell-free experiments. It inhibits formation of hydroxyl radical (Motohashi and Mori, 1986), and superoxide anions (Cargnoni et al, 1995), singlet oxygen at ASPET Journals on May 11, 2018 jpet.aspetjournals.org production (Obayashi et al, 2005), lipid peroxidation (Deiana et al, 2004), and peroxynitrite oxidative damage (Aruoma et al, 1997). As opposed to other naturally occurring thiols (e.g., glutathione, N-acetylcysteine), ergothioneine is present in aqueous solutions predominantly as a thione rather than a tautomeric thiol structure.…”

Antioxidants and Skin Aging

“…In cultured fibroblasts, ergothioneine suppresses the UVBinduced upregulation of tumor necrosis factor-a. In addition, ergothioneine suppresses the expression of MMP-1 protein in fibroblasts exposed to UVA by quenching 1 O 2 (Obayashi et al 2005). Zn(II)-glycine, a coordinated compound of Zn 2+ and glycine, which is a cellmembrane permeable inducer of metallothionein and GSH, protects against UVBinduced cell damage and also suppresses IL-1a secretion and prostaglandin E 2 synthesis in human keratinocytes (Ochiai et al 2008).…”