International Journal of Molecular Medicine · 2019 · 42 citations · 25 references
Life SciencesBiochemistryPharmacologyApoptosisInnate ImmunityRedox BiochemistryAntioxidant DefenseOxidative Damage To BiomoleculesOxidative StressOxidative Stress MechanismsReactive Oxygen SpeciesRedox SignalingHeme Oxygenase PathwayHeme Oxygenase SignalingHeme Oxygenase-1Hydrogen Peroxide TreatmentMelanocyte BiologyNrf2 Pathway ActivationNrf2 Signaling PathwayOxidative Stress Defense
Oxidative stress serves a critical role in melanocyte death and is considered to be a major cause of vitiligo. The nuclear factor E2‑related factor 2 (Nrf2) signaling pathway has an important role in the antioxidative stress mechanisms of melanocytes. Glycyrrhizin (GR) is a derivative of herbal medicines used to treat hepatitis and allergic disease due to its antiviral and anti‑allergy effects. GR also activates Nrf2 and induces the expression of heme oxygenase (HO)‑1 in macrophages. Whether GR can protect human melanocytes from oxidative stress remains unknown. The present study investigated the potential protective effects of GR against oxidative stress in human melanocytes and the mechanisms involved. Following exposure to 0.5 mM hydrogen peroxide (H2O2), human primary melanocytes were treated with 1 mM GR. Cell viability was determined using a Cell Counting Kit‑8 assay, and apoptosis was evaluated by flow cytometry. GR treatment significantly improved cell viability, reduced the apoptotic rate of melanocytes and reduced the level of reactive oxygen species in human melanocytes. Furthermore, GR induced the nuclear translocation of Nrf2 and induced the expression of HO‑1 in melanocytes. The knockdown of Nrf2 by small interfering RNA or the inhibition of HO‑1 by ZnPP reversed the protective effect of GR on melanocytes against H2O2‑induced cytotoxicity and apoptosis. These data demonstrate that GR protects human melanocytes from H2O2‑induced oxidative damage via the Nrf2‑dependent induction of HO‑1, providing evidence for the application of GR in the treatment of vitiligo.
25
Mutation of the mouse klotho gene leads to a syndrome resembling ageing.
PubMed · 1997 · 66.6K citations
Phosphorylation of p62 Activates the Keap1-Nrf2 Pathway during Selective Autophagy
Yoshinobu Ichimura, Satoshi Waguri, Yu‐shin Sou et al. · Molecular Cell · 2013 · 1.2K citations · Full text