Occupational Environment Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Fars, Iran.
Department of Toxicology and Pharmacology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.
Toxicol In Vitro. 2022 Mar;79:105282. doi: 10.1016/j.tiv.2021.105282. Epub 2021 Nov 29.
Many environmental pollutants, natural compounds, as well as endogenous chemicals exert their biological/toxicological effects by reacting with the aryl hydrocarbon receptor (AhR). Previous evidence shed new light on the role of AhR in skin physiology by regulating melanin production. In this study, we investigated the effect of oxidative imbalance induced by AhR ligands on the melanogenesis process in B16 murine melanoma cells. Exposure to 6-formylindolo[3,2-b] carbazole (FICZ) or benzo-α-pyrene (BαP) led to enhanced expression of CTNNB1, MITF, and TYR genes following increased tyrosinase enzyme activity and melanin content in an AhR-dependent manner. Analysis of the presence of reactive oxygen species (ROS) as well as reduced glutathione (GSH) / oxidized glutathione (GSSG) ratio revealed that treatment with AhR ligands is associated with oxidative stress which can be ameliorated with NAC (N-acetyl cysteine) or diphenyleneiodonium chloride (DPI). On the other hand, NAC and DPI enhanced melanogenesis induced by AhR ligands by reducing the level of ROS. We have shown for the first time that a cellular redox status is a critical event during AhR ligand-induced melanogenesis.
许多环境污染物、天然化合物以及内源性化学物质通过与芳香烃受体 (AhR) 反应来发挥其生物/毒性作用。先前的证据通过调节黑色素生成，揭示了 AhR 在皮肤生理学中的作用。在这项研究中，我们研究了 AhR 配体引起的氧化失衡对 B16 鼠黑色素瘤细胞中黑色素生成过程的影响。暴露于 6-甲酰基吲哚并[3,2-b]咔唑 (FICZ) 或苯并-α-芘 (BαP) 以 AhR 依赖性方式导致细胞色素酶活性和黑色素含量增加，从而导致 CTNNB1、MITF 和 TYR 基因的表达增强。对活性氧 (ROS) 和还原型谷胱甘肽 (GSH)/氧化型谷胱甘肽 (GSSG) 比值的分析表明，AhR 配体的处理与氧化应激有关，而 NAC（N-乙酰半胱氨酸）或二苯基碘 (DPI) 可以减轻这种应激。另一方面，NAC 和 DPI 通过降低 ROS 水平增强了 AhR 配体诱导的黑色素生成。我们首次表明，细胞氧化还原状态是 AhR 配体诱导的黑色素生成过程中的一个关键事件。
