Laboratorio di Genetica Molecolare, Istituto Giannina Gaslini, and Centro di Biotecnologie Avanzate, 16148 Genoa, Italy.
Published: April 2007
AI Article Synopsis
Article Abstract
The cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein that belongs to the same family as multidrug resistance-associated proteins whose main function is to expel xenobiotics and physiological organic anions from the cell interior. Despite the overall structural similarity with these membrane proteins, CFTR is not an active transporter but is instead a Cl- channel. We have tested the ability of known inhibitors of multidrug resistance-associated proteins to affect CFTR Cl- currents. We have found that sulfinpyrazone, probenecid, and benzbromarone are also inhibitors of CFTR activity, with a mechanism involving blockage of the channel pore.
Introduction: The plasma membrane-bound protein, multi-drug resistance-associated protein 4 (), has gained attention for its pivotal role in facilitating the efflux of a wide range of endogenous and xenobiotic molecules. Its significance in adipogenesis and fatty acid metabolism has been brought to light by recent studies. Notably, research on knockout ( ) mice has established a link between the absence of and the development of obesity and diabetes.
Background: Microbiota-derived toxins indoxyl sulfate and hippuric acid were previously reported to be associated with altered pharmacokinetics of the immunosuppressant tacrolimus in liver transplant recipients, and ABC transporter proteins are likely to be involved in the transport of such substances, but the role has not been elucidated. The aim of this study was to assess the retention of indoxyl sulfate and hippuric acid in the plasma of liver transplantation subjects carrying different genotypes of and (changes in transporter activity due to genetic variation), and to explore whether genetic variation is involved in altering the relationship between microbe-derived toxins and tacrolimus pharmacokinetics.
Methods: Liver transplantation subjects treated with the immunosuppressive regimen tacrolimus, corticosteroids, and mycophyolate mofetil were included and divided into normal renal function group and chronic kidney disease group.
Chemo-resistance in ovarian cancer is currently a major obstacle to the treatment and recovery of ovarian cancer. Therefore, identifying factors associated with chemo-resistance in ovarian cancer may reverse chemo-sensitization. Using isobaric tags for relative and absolute quantitation (ITRAQ) technology, we found a small molecule peptide with annexin 1 (ANXA1) as a precursor protein.
Raloxifene has low bioavailability due to extensive glucuronidation in the intestine and the liver, and its pharmacokinetics is associated with high intra- and interindividual variability. Some of this variability could be explained by the enterohepatic recycling of raloxifene, which is driven by transporter-mediated uptake and efflux and gut microbial deglucuronidation of raloxifene glucuronides. These individual processes involved in raloxifene disposition, however, have not been characterized in full detail.
Breast cancer is one of the most common cancers among women. Nowadays postoperative adjuvant chemotherapy is the mainstay for clinical treatment of breast cancer. However, the emergence of multidrug resistance (MDR) in breast cancer has become a main reason for the failure of clinical chemotherapy.
