Study On The Role Of P-glycoprotein In The Metabolism Of Cadmium In Meretrix Meretrix

Due to the rapid industrialization and urbanization, heavy metal pollution of seawater has emerged as an important issue that threats the safety of aquatic products. Of the heavy metals, cadmium (Cd) is regarded as the most toxic one. Bivalves have very poor mobility and can accumulate extremely high levels of Cd in their soft tissues. Hence, heavy pollution of bivalves has been accepted as a potential threat of human health. Therefore, it is urgent to develop effective measures to reduce heavy metal residues in bivalves.Aquatic organisms have developed an effective defensive system termed Multixenobiotic resistance (MXR) that is similar to the multi-drug resistance (MDR) of cancer cells. MXR can pump various endogenous and exogenous toxins out of cell and is recognized as the first defense line of cells. MXR consists of multiple transmembrane proteins, of which, p-glycoprotein (P-gp) plays the most important role in metal expulsion. Extensive researches have been performed on the functions of P-gp in Cd bioaccumulation in bivalves, but its role in Cd depuration has not been investigated. Hence, the purpos of this study is to investigate whehter P-gp plays any role in Cd depuration from bivalves.To select a suitable bivalve model for P-gp activity research, the Cd bioaccumulation and depuration capabilities of four common bivalves, including Meretrix meretrix, Mytilus edulis, Scapharca subcrenata, and Crassostrea gigas, were compared in different Cd exposure concentrations (0, 1, 25, and 100μg/L). It is found that the all the four bivalves have strong Cd bioaccumulation, of which, Crassostrea gigas has the highest bioaccumulation factor, followed by Scapharca subcrenata, Mytilus edulis, and Meretrix meretrix in sequence. All the bivalves, except Meretrix meretrix, showed resistance in the early stage of Cd exposure. Because Scapharca subcrenata have strong Cd bioaccumulation capabilities (with BCF in 1, 25, and 100μg/L Cd of 9751, 655, and 296 respectively on day 14) and exhibited active water filtration, Scapharca subcrenata was selected as the model for further study.The role of P-gp in Cd accumulation and depuration of Scapharca subcrenata was investigated by using P-gp's specific inhibitor verapamil. The results showed that P-gp plays important role in both the accumulation and depuration of Cd. In Cd accumulation, 1μg/L and 20μg/L verapamil significantly increased the Cd content in Scapharca subcrenata when exposed to 1μg/L Cd. The changes of P-gp activity, metallothionein, and malondialdehyde contents verified the effects the P-gp. During depuration, the addition of P-gp significantly inhibited Cd depuration from Scapharca subcrenata and the function is evidenced by MDA contents.The conclusion of this research is meaningful for the research of bivalve safety. Though the role of P-gp in Cd bioaccumulation has been recognized, whether it is also involved in Cd depuration is not reported yet. This article confirms for the first time that P-gp plays important role in Cd depuration. If the P-gp activity of bivalves can be improved in proper ways, the Cd depuration process can be accelerated and the Cd residue can be reduced to accepted level in a short time. Hence, this research paves a theory basis for bivalve depuration on the molecular level.