Current Drug Targets - Volume 12, Issue 5, 2011

The superfamily of ABC transporters comprises 49 proteins in humans. They all use ATP hydrolysis as an energy source and share common structural features. In particular, the presence of 2 membrane-spanning domains made of 6 transmembrane segments and of 2 ATP binding cassettes is required to make them functional. Yet, the function of many of these proteins still needs to be elucidated and their substrate Read More

Nine proteins of the ABC superfamily (P-glycoprotein, 7 MRPs and BCRP) are involved in multidrug transport. Being localised at the surface of endothelial or epithelial cells, they expel drugs back to the external medium (if located at the apical side [P-glycoprotein, BCRP, MRP2, MRP4 in the kidney]) or to the blood (if located at the basolateral side [MRP1, MRP3, MRP4, MRP5]), modulating thereby their absorption, distribution, Read More

ATP-binding cassette (ABC) transporters, P-glycoprotein (P-gp, ABCB1) and ABCG2, are membrane proteins that couple the energy derived from ATP hydrolysis to efflux many chemically diverse compounds across the plasma membrane, thereby playing a critical and important physiological role in protecting cells from xenobiotics. These transporters are also implicated in the development of multidrug resistance (MDR) in can Read More

The ATP-binding cassette (ABC) transporter superfamily comprises membrane proteins that translocate a variety of substrates across extra- and intra-cellular membranes, and act as efflux proteins. ABC transporters are characterised by the presence of genetic polymorphisms mainly represented by single nucleotide polymorphisms (SNPs), some of which having an impact on their activity. Besides physiological substan Read More

Atherosclerosis has been characterized as a chronic inflammatory response to cholesterol deposition in arteries. Plasma high density lipoprotein (HDL) levels bear a strong independent inverse relationship with atherosclerotic cardiovascular disease. One central antiatherogenic role of HDL is believed to be its ability to remove excessive peripheral cholesterol back to the liver for subsequent catabolism and excretion, a physiol Read More

Bile formation is a key function of the liver and is driven by active secretion of bile salts and other organic compounds into the biliary tree. Bile salts represent the major organic constituent of bile. They are released with bile into the small intestine, where they are almost quantitatively reabsorbed and transported via the portal circulation back to the liver. In the liver, they are taken up into hepatocytes and secreted into Read More

The ABCC6 gene encodes an organic anion transporter protein, ABCC6/MRP6. Mutations in the gene cause a rare, recessive genetic disease, pseudoxanthoma elasticum, while the loss of one ABCC6 allele is a genetic risk factor in coronary artery disease. We review here the information available on gene structure, evolution as well as the present knowledge on its transcriptional regulation. We give a detailed description o Read More

Several novel compounds recently appeared as promising leads to develop effective drugs against the basic defect in Cystic fibrosis (CF) and the first rationale therapies for CF relying on the understanding of the basic defect started to hit the clinical setting. Most of these efforts are focused on correcting the F508del mutation (occurring in ∼90% of CF patients) which causes misfolding of the CF transmembrane conductance r Read More

Peroxisomes are involved in a variety of metabolic processes, including β-oxidation of fatty acids, especially very long chain fatty acids. Three peroxisomal ABC proteins belonging to subfamily D have been identified in mammalian peroxisomes that have an important role in fatty acid metabolism. ABCD1/ALDP and ABCD2/ALDRP are suggested to be involved in the transport of very long chain acyl-CoA, and ABCD3/PMP Read More

Calcium is a ubiquitous signal molecule and critical to cell function. Maintaining calcium homeostasis is essential to life. Calcium homeostasis is mediated by a number of plasma membrane and intracellular calcium channels and transporters that are driven by stimuli that allow rapid alterations in release and uptake [1]. A large electrochemical gradient is created across the plasma membrane as a result of the differe Read More

The ryanodine receptor (RyR) calcium release channel is an essential intracellular ion channel that is central to Ca2+ signaling and contraction in the heart and skeletal muscle. The rapid release of Ca2+ from the internal sarcoplasmic reticulum Ca2+ stores through the RyR during excitation-contraction coupling is facilitated by the unique arrangement of the surface and sarcoplasmic reticulum membrane systems. Debilitatin Read More

Mammals contain 28 genes encoding Transient Receptor Potential (TRP) proteins. The proteins assemble into cationic channels, often with calcium permeability. Important roles in physiology and disease have emerged and so there is interest in whether the channels might be suitable therapeutic drug targets. Here we review selected members of three subfamilies of mammalian TRP channel (TRPC5, TRPM2 and TRPA Read More

The Na+/Ca2+ exchanger (NCX) is the main Ca2+ extrusion mechanism of the cardiac myocyte and thus is crucial for maintaining Ca2+ homeostasis. It is involved in the regulation of several parameters of cardiac excitation contraction coupling, such as cytosolic Ca2+ concentration, repolarization and contractility. Increased NCX activity has been identified as a mechanism promoting heart failure, cardiac ischemia an Read More

Calcium is a key determinant of cardiac excitation, contraction and relaxation. Cardiac excitation and contraction are powered by ATP that is synthesized within mitochondria via a calcium-dependent process known as oxidative phosphorylation. During this process oxygen molecules within the mitochondria are converted to superoxide. Under physiological conditions, low levels of ROS are required to maintain normal cellula Read More