Glutathione Trisulfide Protects Human Epidermal Keratinocytes from UVB-Induced Damage via Restoration of Intracellular Supersulfide Levels
- 1Research and Development Group, Cosmetics Division, Mitsubishi Corporation Life Sciences Limited, 5th Floor, GranTokyo South Tower, 1-9-2 Marunouchi, Chiyoda-ku, Tokyo 100-6605, Japan
- 2Research and Development Division, Mitsubishi Corporation Life Sciences Limited, 1-1-3 Yurakucho, Chiyoda-ku, Tokyo 100-0006, Japan
Abstract
Ultraviolet B (UVB) irradiation induces oxidative stress and inflammation in keratinocytes, contributing to skin damage and photoaging. Although supersulfides have recently emerged as important regulators of cellular redox homeostasis, their role in UVB-induced skin damage remains poorly understood. In this study, we investigated the effects of glutathione trisulfide (GSSSG), a representative supersulfide, in UVB-exposed normal human epidermal keratinocytes (NHEKs). UVB irradiation significantly reduced cell viability and intracellular supersulfide levels while increasing reactive oxygen species (ROS) production and the expression of IL-1α, prostaglandin E2, and p21. Pretreatment with GSSSG significantly restored intracellular supersulfide levels, improved cell viability, suppressed ROS accumulation and inflammatory mediator production, and attenuated p21 induction. Furthermore, GSSSG significantly promoted nuclear factor erythroid 2-related factor 2 nuclear translocation and increased heme oxygenase-1 production, indicating activation of antioxidant defense pathways. Knockdown of cysteinyl-tRNA synthetase 2 (CARS2), a key enzyme involved in endogenous supersulfide biosynthesis, increased cellular susceptibility to UVB-induced cytotoxicity, whereas GSSSG restored the viability of CARS2-deficient cells. Collectively, these findings suggest that GSSSG protects keratinocytes against UVB-induced oxidative stress, inflammation, and cytotoxicity. This protective activity may be mediated, at least in part, through restoration of intracellular supersulfide levels and activation of the NRF2-mediated antioxidant response.
Related
- Intracellular glutathione availability, rather than vitamin C supplementation, determines endothelial cell resistance to water-soluble cigarette smoke toxicants
- Keratinocytes and PDGF-B/PDGFRβ signaling modulate peripheral opioid tolerance
- Modulating aging-associated phenotypes in keratinocytes using antisense oligonucleotides targeting glycogenes.
- Targeting EGR1 Attenuates CCL2 Expression in Inflammatory Keratinocytes and Allergic Skin Inflammation
- Spartina anglica extract attenuates TNF-α/IFN-γ-induced inflammatory responses in HaCaT keratinocytes through suppression of the MAPK, NF-κB, and STAT1 signaling pathways
BibTeX
@article{uchida2026glutathione,
title = {{Glutathione Trisulfide Protects Human Epidermal Keratinocytes from UVB-Induced Damage via Restoration of Intracellular Supersulfide Levels}},
author = {Yoshiaki Uchida and Keigo Amari and Masayuki Ito and Toshiya Sato},
journal = {Molecules},
year = {2026},
month = oct,
doi = {10.3390/molecules31213871},
url = {https://www.mdpi.com/1420-3049/31/21/3871},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Glutathione Trisulfide Protects Human Epidermal Keratinocytes from UVB-Induced Damage via Restoration of Intracellular Supersulfide Levels
AU - Yoshiaki Uchida
AU - Keigo Amari
AU - Masayuki Ito
AU - Toshiya Sato
PY - 2026
DA - 2026/10/27
JO - Molecules
DO - 10.3390/molecules31213871
UR - https://www.mdpi.com/1420-3049/31/21/3871
AB - Ultraviolet B (UVB) irradiation induces oxidative stress and inflammation in keratinocytes, contributing to skin damage and photoaging. Although supersulfides have recently emerged as important regulators of cellular redox homeostasis, their role in UVB-induced skin damage remains poorly understood. In this study, we investigated the effects of glutathione trisulfide (GSSSG), a representative supersulfide, in UVB-exposed normal human epidermal keratinocytes (NHEKs). UVB irradiation significantly reduced cell viability and intracellular supersulfide levels while increasing reactive oxygen species (ROS) production and the expression of IL-1α, prostaglandin E2, and p21. Pretreatment with GSSSG significantly restored intracellular supersulfide levels, improved cell viability, suppressed ROS accumulation and inflammatory mediator production, and attenuated p21 induction. Furthermore, GSSSG significantly promoted nuclear factor erythroid 2-related factor 2 nuclear translocation and increased heme oxygenase-1 production, indicating activation of antioxidant defense pathways. Knockdown of cysteinyl-tRNA synthetase 2 (CARS2), a key enzyme involved in endogenous supersulfide biosynthesis, increased cellular susceptibility to UVB-induced cytotoxicity, whereas GSSSG restored the viability of CARS2-deficient cells. Collectively, these findings suggest that GSSSG protects keratinocytes against UVB-induced oxidative stress, inflammation, and cytotoxicity. This protective activity may be mediated, at least in part, through restoration of intracellular supersulfide levels and activation of the NRF2-mediated antioxidant response.
SN - 1420-3049
ER -