Interactive effects of nickel and chlorpyrifos on Mediterranean mussel cAMP-mediated cell signaling and MXR-related gene expressions

The aim of this study was to infer putative interactive effects of a binary mixture between nickel (Ni) and chlorpyrifos (CHP) on mussel cell signaling, and also to unravel downstream effects on transcriptional regulation mediating cytoprotective responses. Mussels were exposed for 4 days to Ni (0.77 mg/L), CHP (4.5 mg/L), or the mixture Ni/CHP (0.135 mg/L Ni and 0.61 mg/L CHP). Cyclic AMP content and PKA activity in gills were evaluated as biological endpoints related to cell signaling. Expression of the MgPgp (ABCB1) and MgMvp genes was also assessed as involved in the mussel MXR mechanism. Levels of cAMP and PKA activities were not modified in mussels exposed to Ni or CHP, whereas they significantly increased in organisms exposed to the mixture. Similar responses were also detected for MgPgp expression, which is thought to be under cAMP/PKA-mediated regulation. Expression of MgMvp was unaffected by CHP or Ni/CHP exposure, and increased by Ni. The differential regulation of MgPgp and MgMvp expressions could be ascribed to the different intracellular localization and function of the two transporters. On the whole, present data indicated that Ni and CHP elicited interactive effects on mussel physiology, both at the signal transduction and at the gene expression levels.