Phenanthrene-Induced Apoptosis and Its Underlying Mechanism

Abstract

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.

The long noncoding RNA GAS5 negatively regulates the adipogenic differentiation of MSCs by modulating the miR-18a/CTGF axis as a ceRNA

“…MicroRNA-18a is an important member of the miR-17-92 cluster that plays a carcinogenic role in some tumors 19 – 21 and is important for differentiation and apoptosis 22 , 23 . Connective tissue growth factor (CTGF), a member of a family of cysteine-rich matricellular proteins, recently emerged as a multifunctional regulator because it controls diverse cellular processes, as well as vascular and skeletal development 24 – 26 .…”

Comparison of the Toxicity Effects of Tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) with Tributyl Phosphate (TNBP) Reveals the Mechanism of the Apoptosis Pathway in Asian Freshwater Clams (Corbicula fluminea)

“…The activities of three caspases (caspases 3, 8, and 9) were determined using caspase activity kits according to the manufacturer’s instructions (Beyotime, Nanjing, China) . Briefly, the digestive glands of six clams were homogenized and centrifuged at 4 °C and 16 000 g for 15 min.…”

“…The apoptotic cells in sections of the digestive gland were detected using the TUNEL assay . Briefly, the samples from six clams were fixed in 4% paraformaldehyde at 4 °C for 24 h, dehydrated, embedded in paraffin, and cut into 5-mm-thick sections.…”

“…The activities of three caspases (caspases 3, 8, and 9) were determined using caspase activity kits according to the manufacturer's instructions (Beyotime, Nanjing, China). 38 Briefly, the digestive glands of six clams were homogenized and centrifuged at 4 °C and 16 000g for 15 min. The reaction solution consisted of a mixture of 50 μL of supernatant (controlled tubes were added to 50 μL of lysis buffer), 40 μL of test buffer, and 10 μL of the substrate.…”

Behavioural, Histopathological, Genetic and Organism-Wide Responses to Phenanthrene-Induced Oxidative Stress in Eisenia Fetida Earthworms in Natural Soil Microcosms

“…It is estimated that annually about 29,190 tons of phenanthrene are released into the environment (He et al 2021a). Exposure to and toxicity from PHE has been reported in human and aquatic organisms (Hong et al 2017). Moreover, PHE exhibited potential threats to soil invertebrates such as earthworms (Andreoni et al 2004;Picariello et al 2020;He et al 2021a).…”