The tolerance mechanism of diarrhetic shellfish toxins mediated by the extracellular regulated protein kinase (ERK) pathway in the mussel Perna viridis

Abstract

Diarrheic shellfish toxins (DSTs) are a class of lipophilic algal toxins that accumulate excessively in bivalves following harmful algal blooms. Bivalves exhibit tolerance to DSTs, which make people ignore or underestimate the risk of DSTs, leading to the occurrence of seafood poisoning incidents. However, the tolerance mechanism remains unclear in bivalves. We investigated the role of extracellular-regulated protein kinase (ERK) in DSTs tolerance, observed that the ERK inhibitor PD98059 exacerbated damage of DSTs to the digestive tubules. PD98059 induced the TUNEL fluorescence intensity, and caspase-3 activity inhibited by DSTs were restored to the control. PD98059 enhanced the fluorescence intensity of extracellular Ca-AM and increased the accumulation of esterified DSTs. Transcriptome analysis revealed that PD98059 affected the genes expression related to apoptosis, ABC transporters, and lipid metabolism. qPCR analysis demonstrated that PD98059 down-regulated the DSTs-induced iap and ABCC10 (p = 0.063), and up-regulated ABCB1-like1, ABCC1, ABCC1-like1, and ABCC9. Molecular docking suggested that ABCC10 exhibited high affinity for esterified okadaic acid. Overall, ERK plays a crucial role in DSTs tolerance by regulating the anti-apoptotic system and ABC transporters in bivalves. Our study is of great significance to understand the tolerance mechanism in bivalves and the safety risk caused by DSTs.