ABSTRACT
In response to stress, cells can utilize several processes, such as the activation of the Nrf2/Keap1 pathway as a critical regulator of oxidative stress to protect against oxidative damage. C-Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase (MAPK) family, is involved in regulating the NF-E2-related nuclear factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway. NAD(P)H quinone redox enzyme-1 (NQO1), a downstream target gene of the Nrf2 pathway, plays a vital role in removing peroxide and providing resistance to oxidative injury. We found that microcystins (MCs) stimulated CpNrf2 to express and increase anti-oxidative enzyme activities in a previous experiment. In our current study, the full-length cDNAs of JNK and NQO1 from Cristaria plicata (designated CpJNK and CpNQO1) were cloned. The relative levels of CpJNK and CpNQO1 were high in hepatopancreas. Upon MCs induction, the relative level of CpNQO1 was increased, whereas that of CpJNK was decreased significantly. In contrast, CpNrf2 knockdown upregulated the expression of CpJNK mRNA and phosphorylation of CpJNK protein (Cpp-JNK), but inhibited CpNQO1 expression. Additionally, we found that JNK inhibitor SP600125 stimulated expression of CpNQO1 and CpNrf2 upon exposure to MCs, and we further confirmed that CpNrf2 protein combined with the ARE element in CpNQO1 gene promoter in vitro, and increased CpNQO1-ARE-luciferase activity in a CpNrf2-dependent manner. These findings indicated C. plicata effectively alleviated MC-induced oxidative injury through JNK participated in regulating the Nrf2/NQO1-ARE pathway.
