ABC transporter protein

Mulugeta S, Gray JM, Notarfrancesco KL, Gonzales LW, Koval M, Feinstein SI, Ballard PL, Fisher AB, Shuman H (2002) Identification of LBM180, a lamellar body limiting membrane protein of alveolar type II cells, as the ABC transporter protein ABC A3. J Biol Chem 277(25) 22147-22155... 

Figure 17.1 Schematic cross section of a brain capillary formed by endothelial cells which are surrounded by pericytes and foot processes of astrocytes. Endothelial cells express various ABC-transport proteins at their luminal surface which significantly contribute to the barrier function.

Such studies are not limited to studying the interaction of potential substrates with ABC-transport proteins at the luminal membrane of brain capillaries but can also be used to investigate the regulatory mechanisms underlying the expression and function of these proteins as discussed above [72, 75, 78],... 

Membrane transporter proteins (MDR or ABC transporter proteins) such as p-glycoprotein are crucially important in the process of excretion and also in absorption and distribution and elimination of chemicals from cells. These transport organic anions or cations and neutral compounds across membranes, pump unwanted chemicals out of cells such as in gut, placenta, and brain, transport chemicals into bile from liver cells, and facilitate excretion from the kidney. 

ABC transporter proteins are crucial elements in the detoxication process as they pump potentially toxic chemicals out of cells and tissues. Thus the transporters in the intestine pump chemicals back into the lumen of the gut, those in the brain form part of the blood-brain barrier, keeping chemicals out of the organ, as also occurs in the placenta where transporters move chemicals out of the fetal bloodstream and back into the maternal bloodstream. 

Breast Cancer Resistance Protein (BCRP) BCRP is one of the newer ABC transport proteins to be examined. The transporter was first identified in drug-resistant breast cancer cells.165 Structurally, BCRP differs from both P-gp and MRP in that it is a half-transporter and requires the formation of a protein dimer for functional transporter activity.166 There is a great deal of substrate overlap between P-gp and BCRP.167 In addition to being overexpressed in various tumor cells, BCRP has been detected in normal tissues such as the placenta, small intestine, liver, and capillary and venous endothelial cells.156... 

Kamis, A.B. (2005) Purification and electron microscopic studies of two ABC transporter proteins of clinical relevance. PhD thesis. University of Manchester, UK. 

The expression of another ABC transport protein, multidrug resistance-related protein 2 (MRP2) decreases from proximal to distal parts ofthe GI tract [53]. The... 

HDL is antiatherogenic and removes cholesterol from peripheral cells and tissues for eventual transport to hepatocytes and excretion in the bile directly or after conversion into bile acids. The efflux of cholesterol from peripheral cells is mediated by the ATP-binding cassette (ABC) transporter protein (discussed later). The flux of cholesterol transport from extrahepatic tissues (e.g., blood vessel wall) toward liver for excretion is known as the reverse cholesterol transport pathway. In contrast, the forward cholesterol pathway involves the transport of cholesterol from liver to the peripheral cells and tissues via the VLDL IDL LDL pathway. It should be noted, however, that the liver plays a major role in the removal of these lipoproteins. Thus, the system of reverse cholesterol transport consisting of LCAT, CETP, apo D, and their carrier lipoproteins is critical for maintaining cellular cholesterol homeostasis. The role of CETP is exemplified in clinical studies involving patients with polymorphic... 

Cancer patients often take multiple drugs concurrently in the course of chemotherapy, and in many cases cancer cells become simultaneously resistant to many or all of them. This multiple-drug resistance can be due to the proliferation of cancer cells that overexpress a number of ABC transporter proteins that pump drugs out of the cell (p. 358). Thus, cancer cells can evolve drug resistance by overexpressing normal human proteins or by modifying proteins responsible for the cancer phenotype. 

ABC transport proteins enable the cells to import nutrients against substantial concentration gradients. Bacterial permeases generally are Inducible that is, the quantity of a transport protein In the cell membrane is regulated by both the concentration of the nutrient In the medium and the metabolic needs of the cell. 

About 50 different mammalian ABC transport proteins are now recognized (see Table 18-2). These are expressed In... 

Several human genetic diseases are associated with defective ABC proteins. X-llnked adrenoleukodys-trophy (ALD), for Instance, is characterized by a defective ABC transport protein (ABCDl) that is localized to peroxisomal membranes. This protein normally regulates Import of very long chain fatty acids into peroxisomes, where they undergo oxidation in its absence these fatty acids accumulate in the cytosol and cause cellular damage. Tanglers disease is marked by a deficiency of the plasma-membrane ABC protein (ABCAl) that transports phospholipids and possibly cholesterol (Chapter 18). 

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