The role of the multixenobiotic resistance mechanism (MXR), p-glycoprotein, as a protective mechanism against environmental stress in Mytilus mussels

A multixenobiotic resistance mechanism (MXR) related to the mammalian p-glycoprotein (p-gp) multidrug resistance transporter has been identified and characterized in the mussel Mytilus californianus. MXR functions in extruding compounds from the cell, presumably providing the cell with toxicant protection. M. californianus express abundant p-gp activity in the gills, a tissue with potentially high toxicant exposure due to its filtering function. The role of p-gp as a first line of toxicant defense was assessed by describing p-gp substrates in the natural habitat, examining seasonal fluctuations in p-gp activity, measuring the induction of the p-gp response and characterizing the expression and protective role of p-gp in mussel embryos. Extracts of various seaweeds and phytoplankton that constitute part of the mussel diet showed p-gp modulating ability, suggesting a possible reason for the presence of high p-gp activity in the mussel gill. Extracts of Egregia menziesii also blocked the transport function of p-gp in mussel embryos, causing slowed development in the presence of the cytotoxic p-gp substrate vinblastine. P-gp expression in mussel gills showed a seasonal increase in constitutive p-gp and decrease in p-gp inducibility that was related to ocean temperature. Controlled laboratory studies supported this association between temperature and p-gp expression, however, other factors such as algal composition may also play a role in seasonal p-gp fluctuations. In addition to natural seasonal fluctuations, p-gp expression was responsive to several environmental stresses including heat shock, heavy metals and organic toxicant exposure, indicating that it is a general stress response. There was no consistent trend between induction of p-gp and another general stress response, hsp70, suggesting that the two mechanisms might constitute distinct response pathways. Finally, p-gp expression was shown to be present early in development from unfertilized egg on. In the potentially vulnerable early developmental stages, p-gp conferred toxicant protection from p-gp substrates but not from non-substrate toxicants. Taken together these results suggest that p-gp acts as a first line of defense, protecting the mussel at all developmental stages from a broad range of natural and anthropogenic stresses.