Phenanthrene-Induced Apoptosis and Its Underlying Mechanism

• Published in: Environmental science & technology Vol. 51; no. 24; pp. 14397 - 14405
• Main Authors: Hong, Xiangsheng, Qin, Jianhui, Chen, Rui, Yuan, Lilai, Zha, Jinmiao, Huang, Chao, Li, Na, Ji, Xiaoya, Wang, Zijian
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 19.12.2017
• Subjects: Animals; Apoptosis; Caspase; Caspase-3; Caspase-9; Chronic effects; Cyprinidae; Enzymatic activity; Enzyme activity; Exposure; Gene expression; Hepatocytes; Hepatotoxicity; Histopathology; Humans; Lesions; Liver; Membrane potential; Mitochondria; Molecular docking; Molecular Docking Simulation; Molecular weight; Phenanthrene; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Tissues; Toxicity
• ISSN: 0013-936X; 1520-5851
• DOI: 10.1021/acs.est.7b04045

Phenanthrene (Phe) is one of the most abundant low-molecular-weight polycyclic aromatic hydrocarbons (PAHs). Widespread human and aquatic organism exposure to Phe has been reported, but the toxic effects of Phe and potential mechanisms are unclear. We focused on the chronic hepatotoxicity of Phe in adult Chinese rare minnows (Gobiocypris rarus) and the underlying mechanisms. The chronic effects of exposing Chinese rare minnows to 8.9, 82.3, or 510.0 μg/L Phe for 30 days were examined by histopathological observation, TUNEL assays, caspase activity assays, and gene expression profiles. The liver lesion frequency and hepatocyte apoptosis were increased in Phe-exposed groups. Caspase 9 and caspase 3 enzyme activity in liver tissues was markedly increased. The expression of miR-17/92 cluster members was significantly increased in the 82.3 and 510.0 μg/L groups. Moreover, the response of primary hepatocytes indicated a significant decrease in the mitochondrial membrane potential (MMP) after a 48 h exposure to Phe. Interestingly, miR-18a was significantly decreased in primary hepatocytes in all treatments. Moreover, molecular docking indicated that Phe might have the same binding domain as pri-miR-18a, forming pi-pi and pi-σ interactions with heterogeneous nuclear ribonucleoprotein (hnRNP) A1. Given the above, Phe caused liver lesions and induced hepatocyte apoptosis through the intrinsic apoptosis pathway, and the interaction of Phe with hnRNP A1 contributes to the suppression of miR-18a expression and hepatocyte apoptosis.