Search results for "Porters"
showing 10 items of 233 documents
Inhibition of tumor lactate oxidation: consequences for the tumor microenvironment.
2011
Abstract Background and purpose Tumor cells are recognized as being highly glycolytic. However, recently it was suggested that lactate produced in hypoxic tumor areas may be taken up by the monocarboxylate transporter MCT1 and oxidized in well-oxygenated tumor parts. Furthermore, it was shown that inhibition of lactate oxidation using the MCT1 inhibitor α-cyano-hydroxycinnamate (CHC) can radio-sensitize tumors possibly by forcing a switch from lactate oxidization to glycolysis in oxygenated cells, which in turn improves tumor oxygenation and indirectly kills radio-resistant hypoxic tumor cells from glucose starvation. Material and methods To provide direct evidence for the existence of a ta…
Lactaturia and loss of sodium-dependent lactate uptake in the colon of SLC5A8-deficient mice.
2008
SLC5A8 is a member of the sodium/glucose cotransporter family. It has been proposed that SLC5A8 might act as an apical iodide transporter in the thyroid follicular cells or as a transporter of short chain monocarboxylates. We have directly addressed the functional role of SLC5A8 in vivo by generation of SLC5A8 mutant mice. We found that SLC5A8 is responsible for the re-absorption of lactate at the apical membrane of the kidney proximal tubules and of serous salivary gland ducts. In addition, SLC5A8 mediated the uptake of lactate into colonocytes under physiological conditions. We did not find any evidence of SLC5A8 being essential for the apical iodide transport in the thyroid gland, even i…
Novel mutations of the ABCA12, KRT1 and ST14 genes in three unrelated newborns showing congenital ichthyosis.
2022
Abstract Background Congenital ichthyosis (CI) is a heterogeneous group of genetic disorders characterized by generalized dry skin, scaling and hyperkeratosis, often associated to erythroderma. They are rare diseases, with overall incidence of 6.7 in 100,000. Clinical manifestations are due to mutations in genes mostly involved in skin barrier formation. Based on clinical presentation, CI is distinguished in non-syndromic and syndromic forms. To date, mutations of more than 50 genes have been associated to different types of CI. Cases presentation We report on three Italian unrelated newborns showing clinical signs compatible with different forms of CI of variable severity, namely Harlequin…
The loss of the inducible Aspergillus carbonarius MFS transporter MfsA leads to ochratoxin A overproduction
2014
Ochratoxin A (OTA), a nephrotoxic compound produced by certain Aspergillus and Penicillium species, is one of the most abundant mycotoxins in food commodities. Aspergillus carbonarius is the main source of OTA in wine, grape juice and dried vine fruits. Although many studies have focused on OTA production by A. carbonarius, little is known about the genes related to OTA production and transport. We have found a transporter that belongs to the major facilitator superfamily (MfsA) which is highly expressed with a 102-fold induction in an ochratoxigenic A. carbonarius strain compared to a low OTA producer strain. The encoding mfsA gene shows similarity to the multidrug efflux transporter flu1 …
A comprehensive review of the clinical utility of and a combined analysis of the clozapine/norclozapine ratio in therapeutic drug monitoring for adul…
2019
Introduction: This article comprehensively reviews the clinical utility of the serum clozapine/norclozapine (CLO/NCLO) ratio. Areas covered: Fifty-four published studies used this ratio (21 from a PubMed search from onset to 10/21/18 and 33 identified by the authors). To estimate a combined mean of the CLO/NCLO ratio in published studies, a PubMed search on 10/21/18 identified 422 articles leading to 19 included. The systematic review focused on 1) the combined analysis, 2) CYP1A2 activity, 3) clinical response, 4) cognition, and 5) renal function. Expert opinion: Our combined analysis provided a weighted mean CLO/NCLO ratio of 1.73 in 2,317 adult patients from 19 studies, but the range in …
Common Breast Cancer Susceptibility Alleles and the Risk of Breast Cancer for BRCA1 and BRCA2 Mutation Carriers: Implications for Risk Prediction
2010
Abstract The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11, and rs10941679 at 5p12, and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased breast cancer risk for BRCA2 carrie…
Regulation of tartrate metabolism by TtdR and relation to the DcuS–DcuR-regulated C4-dicarboxylate metabolism of Escherichia coli
2009
Escherichia coli catabolizes l-tartrate under anaerobic conditions to oxaloacetate by the use of l-tartrate/succinate antiporter TtdT and l-tartrate dehydratase TtdAB. Subsequently, l-malate is channelled into fumarate respiration and degraded to succinate by the use of fumarase FumB and fumarate reductase FrdABCD. The genes encoding the latter pathway (dcuB, fumB and frdABCD) are transcriptionally activated by the DcuS–DcuR two-component system. Expression of the l-tartrate-specific ttdABT operon encoding TtdAB and TtdT was stimulated by the LysR-type gene regulator TtdR in the presence of l- and meso-tartrate, and repressed by O2 and nitrate. Anaerobic expression required a functional fn…
The cytoplasmic PASC domain of the sensor kinase DcuS of Escherichia coli : role in signal transduction, dimer formation, and DctA interaction
2013
The cytoplasmic PAS(C) domain of the fumarate responsive sensor kinase DcuS of Escherichia coli links the transmembrane to the kinase domain. PAS(C) is also required for interaction with the transporter DctA serving as a cosensor of DcuS. Earlier studies suggested that PAS(C) functions as a hinge and transmits the signal to the kinase. Reorganizing the PAS(C) dimer interaction and, independently, removal of DctA, converts DcuS to the constitutive ON state (active without fumarate stimulation). ON mutants were categorized with respect to these two biophysical interactions and the functional state of DcuS: type I-ON mutations grossly reorganize the homodimer, and decrease interaction with Dct…
The stability and functional properties of proteoliposomes mixed with dextran derivatives bearing hydrophobic anchor groups
1992
Liposomes composed of Escherichia coli phospholipid were coated with polysaccharides bearing hydrophobic palmitoyl anchors. The effect on the stability of liposomes without or with integral membrane proteins was investigated. A high concentration of hydrophobized dextrans protected the liposomes against detergent degradation, decreased the fluidity of the membranes, prevented fusion of the liposomes and enhanced their stability. Proteoliposomes containing beef heart cytochrome-c oxidase and the lactose transport carrier of E. coli were similarly affected by coating with the dextrans. Under these conditions both membrane proteins were still active. Long-term stability of the coated liposomes…
Multi-Functional Nanogels for Tumor Targeting and Redox-Sensitive Drug and siRNA Delivery
2016
(1) Background: A new family of nanosystems able to discern between normal and tumor cells and to release a therapeutic agent in controlled way were synthetized by e-beam irradiation. This technique permits to obtain biocompatible, sterile, carboxyl-functionalized polyvinylpyrrolidone (PVP-co-acrylic acid) nanogels (NGs); (2) Methods: Here, we performed a targeting strategy based on the recognition of over-expressed proteins on tumor cells, like the folate receptor. The selective targeting was demonstrated by co-culture studies and flow cytometry analysis, using folate conjugated NGs. Moreover, nanoparticles were conjugated to a chemotherapeutic drug or to a pro-apoptotic siRNA through a gl…