Cui Xiao, Mi Tingyan, Xiao Xue, Dong Yiying, Zhang Hong, Chen Guoqiang, Gu Xuelan
Unilever Research & Development, Shanghai, China.
J Cosmet Dermatol. 2025 Apr;24(4):e70168. doi: 10.1111/jocd.70168.
Pollutant particles can penetrate and accumulate in skin, leading to excessive oxidative stress, inflammation, and skin disorders. Reduced glutathione (GSH) is considered as "the master antioxidant" and major detoxification agent.
To characterize the metabolomic changes of skin keratinocytes under the pollutant benzo[a]pyrene (BaP) challenge and investigate the interventional effects of glutathione amino acid precursors (GAP).
Normal human epidermal keratinocytes (NHEKs) were challenged with BaP with or without GAP treatment. GSH/GSSG levels were measured by UPLC-MS/MS. Non-targeted metabolome analysis was conducted with UPLC-QTOF mass spectrometry. Transcriptomics analysis was performed using RNA-seq. DNA damage biomarker γ-H2AX was analyzed by western blot. Reconstructed pigmented skin equivalent models (pLSE) were used for evaluating phenotypical changes.
One micromolar BaP exposure induced widespread metabolic reprogramming in in vitro NHEKs with over-represented differential metabolites in pathways including purine and pyrimidine nucleotide metabolism, xenobiotic metabolism, methylation, and RNA modification, etc. GAP co-treatment improved GSH/GSSG ratio, reduced reactive BaP metabolites, and partially reversed BaP induced metabolic and transcriptomic alterations. Western blotting further confirmed that GAP treated samples showed reduced γ-H2AX staining. In pLSE models, GAP treatment significantly ameliorated BaP induced skin darkness and hyperpigmentation.
In summary, GAP shows in vitro protective effects against BaP by maintaining GSH homeostasis, helping metabolic detoxification, reducing DNA damage, and is effective in preventing hyperpigmentation of skin models under pollution challenge.
污染物颗粒可穿透并积聚在皮肤中，导致过度的氧化应激、炎症和皮肤疾病。还原型谷胱甘肽（GSH）被认为是“主要抗氧化剂”和主要解毒剂。
表征污染物苯并[a]芘（BaP）刺激下皮肤角质形成细胞的代谢组学变化，并研究谷胱甘肽氨基酸前体（GAP）的干预作用。
用或不用GAP处理，用BaP刺激正常人表皮角质形成细胞（NHEK）。通过超高效液相色谱-串联质谱法（UPLC-MS/MS）测量GSH/GSSG水平。使用超高效液相色谱-四极杆飞行时间质谱仪（UPLC-QTOF）进行非靶向代谢组分析。使用RNA测序进行转录组分析。通过蛋白质印迹法分析DNA损伤生物标志物γ-H2AX。使用重建的色素沉着皮肤等效模型（pLSE）评估表型变化。
1微摩尔BaP暴露在体外NHEK中诱导了广泛的代谢重编程，嘌呤和嘧啶核苷酸代谢、异源物质代谢、甲基化和RNA修饰等途径中的差异代谢物过度富集。GAP联合处理提高了GSH/GSSG比值，减少了活性BaP代谢物，并部分逆转了BaP诱导的代谢和转录组改变。蛋白质印迹进一步证实，GAP处理的样品显示γ-H2AX染色减少。在pLSE模型中，GAP处理显著改善了BaP诱导的皮肤变黑和色素沉着。
总之，GAP通过维持GSH稳态、帮助代谢解毒、减少DNA损伤，在体外对BaP具有保护作用，并且在污染挑战下对预防皮肤模型的色素沉着有效。
