Multi-drug resistance pumps

Little is known of the ways of biosynthesis and insertion in the membranes of PolyP-PHB-Ca2+ complexes. In polyphosphate kinase 1 mutants of E. coli, the amounts of the complexes did not change (Castuma et al., 1995). Therefore, the PolyP in the complexes is synthesized not by polyphosphate kinase 1 but by another enzyme. E. coli strain, which lacks the AcrA component of a major multi-drug resistance pump, had greatly reduced amounts of the complexes and was defective in its ability to maintain sub-micromolar levels of free Ca2+ in the cytoplasm (Jones et al., 2003). This indicates that the AcrAB transporter may have a novel, hitherto undetected, physiological role, either directly in the membrane assembly of the PHB complexes or the transport of a component of the membrane, which is essential for assembly of the complexes into the membrane. 

Bacterial resistance to antibiotics continues to be a significant problem, as microorganisms appear able to develop resistance to new drugs as rapidly as they are introduced. One of the primary means by which microbes become resistant is through the development or enhancement of methods for the extrusion of antibiotics out of the cell via multi-drug resistance (MDR) pumps [98]. The function of microbial MDRs remains a hotly debated subject given the very broad substrate specificities of... 

P-glycoprotein (P-gp) is an ATP-dependent drug efflux pump. In humans, P-gp is encoded by the multi-drug resistance gene (MDR-1) that is located on the long arm of chromosome 7. Overexpression of P-gp in neoplastic cells is associated with the phenomenon of multidrug resistance to chemotherapeutic agents... 

DiOC6 (3) is rapidly removed from the cells that have active efflux pump (P glycoprotein), such as stem cells or multi-drug resistant tumor cells, which may simulate collapse of AW,. 

P-glycoprotein (P-gp), also known as ABCBl, or multi-drug resistance protein 1 (MDRl), is a multi-drug efflux pump (a protein that removes drugs and related compounds from cells) that can move a wide variety of compounds across cellular membranes. P-gp is concentrated in the excretory tissues (liver and kidney) and in barrier tissues (intestines, blood-brain barrier, placental barrier, blood-testes barrier,... 

Efflux pumps are transmembrane located transporter proteins which are expressed in various tissues including liver, placenta, the proximal tubule in the kidney, capillary endothelial cells of brain and testis, and epithelial cells of the intestine [1,2]. In addition, they are over-expressed in cancer cells and are involved in the multi drug resistance (MDR) mechanisms of tumors. Besides other mechanisms such as CYP3A, efflux pumps constitute an integral part of the body s natural detoxification system. Due to their loealisation in various tissue they affect absorption, distribution, metabolism and elimination [3]. They are... 

Chapter 7 - The ability of amphiphilic block copolymers to modulate multi drug resistance related processes has been demonstrated the first time more than 10 years ago. Nowadays, the efflux pump inhibitory activity of amphiphilic block copolymers is used in two main areas. First, to improve the transport of efflux pump substrates across the blood brain barrier (BBB) and second, in cancer therapy. It has been shown that in the presence of amphiphilic block copolymers higher concentrations of certain anticancer drugs, which are... 

---