The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao, 266003, China.
The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao, 266003, China.
Environ Res. 2020 Apr;183:109165. doi: 10.1016/j.envres.2020.109165. Epub 2020 Jan 27.
The aryl hydrocarbon receptor (AhR) has been known primarily for its role in the regulation of several drug and xenobiotic metabolizing enzymes to mitigate environmental stresses. In this study, we interfere the expression of AhR gene to investigate the mechanism of AhR signaling pathway in the detoxification and antioxidation defense system that induced by Polycyclic Aromatic Hydrocarbons (PAHs) exposure by RNA interference (RNAi). The gene expressions of aryl hydrocarbon receptor nuclear translocator (ARNT), heat shock protein 90 (Hsp90) were evaluated after being exposed to benzo(a)pyrene (BaP) (4 μg/L) for 5 days and the positive correlations between AhR, ARNT, HSP90 indirectly indicating that AhR may have the ability to bind to ligands such as PAHs in Ruditapes philippinarum (R. philippinarum). Besides, the activities of detoxification enzymes were determined to investigate the role of AhR signaling pathway played in the metabolic detoxification. What's more, the gene expressions of protein kinase C (PKC) signaling pathway, mitogen-activated protein kinase (MAPKs) signaling pathway, NF-E2-related factor 2 (Nrf2) signaling pathway and antioxidant defense system indicated that AhR may regulate the Nrf2-Keap1 signaling pathway through Kelch-like ECH-associated protein-1 (Keap1) and MAPKs, PKC signaling pathways. In conclusion, adoption of RNA interference technology to explore the role of RpAhR gene played in the detoxification and antioxidation defense system under the PAHs stress at different time points can informe molecular endpoints for application towards ecotoxicology monitoring of bivalves.
芳香烃受体 (AhR) 主要因其在调节几种药物和外源性代谢酶中的作用而闻名,以减轻环境压力。在这项研究中,我们通过 RNA 干扰 (RNAi) 干扰 AhR 基因的表达,研究 AhR 信号通路在多环芳烃 (PAHs) 暴露诱导的解毒和抗氧化防御系统中的作用机制。在暴露于苯并(a)芘 (BaP) (4μg/L) 5 天后,评估芳基烃受体核转位蛋白 (ARNT)和热休克蛋白 90 (Hsp90)的基因表达,AhR、ARNT 和 HSP90 之间的正相关间接表明 AhR 可能具有与如在菲律宾蛤仔 (Ruditapes philippinarum) 中结合配体的能力,如多环芳烃 (PAHs)。此外,还测定了解毒酶的活性,以研究 AhR 信号通路在代谢解毒中的作用。更重要的是,蛋白激酶 C (PKC) 信号通路、丝裂原激活蛋白激酶 (MAPKs) 信号通路、核因子 E2 相关因子 2 (Nrf2) 信号通路和抗氧化防御系统的基因表达表明,AhR 可能通过 Kelch 样 ECH 相关蛋白 1 (Keap1) 和 MAPKs、PKC 信号通路调节 Nrf2-Keap1 信号通路。总之,采用 RNA 干扰技术在不同时间点探索 AhR 基因在 PAHs 应激下在解毒和抗氧化防御系统中的作用,可以为贝类生态毒理学监测提供分子终点。