Effects of Nrf2-Keap1 signaling pathway on antioxidant defense system and oxidative damage in the clams Ruditapes philippinarum exposure to PAHs.

NF-E2-related factor 2 (Nrf2) is a master regulator of antioxidant defense system which can maintain the oxidation balance in the cell. In our previous study, we first cloned the Nrf2 gene in clams and preliminarily explored the role of the Nrf2 at the transcription level. In this study, RNA interference (RNAi) technology was used to interfere with the expression of Nrf2 after being exposed to benzo(a)pyrene (BaP) for 5 days to verify the role of Nrf2 in the antioxidant defense system. Besides, we examined the mRNA expression and enzyme activities of antioxidases and the oxidative damage. The positive correlations between the Nrf2 with the mRNA expression and the enzyme activities of antioxidases indicated that Nrf2 was required for the induction of these antioxidant genes. Additionally, the mRNA expression and the enzyme activities of the glutathione peroxidase (GPx) in the Nrf2-dsRNA group were significantly higher than those in the control groups on the fifth day, indicating that the GPx is more sensitive to oxidative stress. Moreover, the oxidative damage in the RpNrf2-dsRNA group was markedly increased than control groups, indicating that Nrf2 transcriptional regulation may play an essential role in defending against oxidative damage. This study provides a foundation for further research on the mechanism of detoxification and antioxidation of polycyclic aromatic hydrocarbons (PAHs) in the clams at the transcription level and the protein level.