ABC transporters are one of the largest families of proteins, and are present in all living organisms, from bacteria to humans. The members of the ABC family are transmembrane proteins (proteins that cross the cell membrane, having a portion inside the cell and another outside) capable of transporting various substrates across the cell membrane, with energy expenditure. In healthy cells, ABC transporters have different functions, such as transporting bile salts, cholesterol, different ions and anions, however, they are also related to the resistance of cancer cells to chemotherapy treatments, they are recognized in a large number of organisms, due to their participation in drug detoxification. They are transmembrane proteins, responsible for removing toxic, endogenous or exogenous compounds from the cell. In this way, they protect organisms and are associated with drug resistance in various nematodes, parasitic arthropods and cancer cells.
The role of ABC transporters in resistance to multiple drugs over the years, several proteins of the ABC transporter family have been discovered that have been shown to induce resistance to multiple drugs in cancer cells, such as P-glycoprotein (Pgp), MDR proteins related ABCC1, ABCG2 and antigenic peptide transporter proteins (TAP). These proteins are capable of removing the molecules of chemotherapeutic drugs from the intracellular medium, transporting them out of the cell, regardless of the concentration of drugs in the extracellular medium, functioning as pumps in exchange for the consumption of ATP (adenosine triphosphate, a nucleotide that stores and supplies energy to cells). As the concentration of drugs inside the cells decreases due to the action of ABC transporters, they become resistant,
Treatment with ABC transporter inhibitors increased the toxicity of ivermectin in larvae and adult females from field populations resistant to this acaricide. ABC transporter inhibitors have also increased the toxicity of abamectin, moxidectin and chlorpyrifos, in a multidrug-resistant population, indicating that these transporters are responsible for detoxifying a large number of structurally unrelated acaricides. Significantly higher levels of transcription of the RmABCB10 gene were identified in the intestine of females from populations resistant to ivermectin and amitraz, compared to the susceptible population, an important indicator of the participation of this ABC transporter in resistance to acaricides. The toxicity of ivermectin was also significantly increased, in a population of embryonic tick cells resistant to this mite, when they were co-incubated with an ABC transporter inhibitor.
In addition, the transcription levels of the RmABCB10 gene were also induced in this same population, compared to parental cells susceptible to ivermectin, indicating that similar mechanisms are selected in vivo and in vitro, and confirming the participation of ABC transporters in ivermectin resistance. We also show that ABC transporters responsible for sequestration and, consequently, detoxification of the heme molecule into the hemosomes, present in the tick intestine, are important in the detoxification of acaricides into the same organelle. Suggesting that this is an important defense mechanism against tick mites.
