Search results for "Efflux"
showing 10 items of 106 documents
Lomitapide affects HDL composition and function
2016
Abstract Background Lomitapide reduces low-density lipoprotein-cholesterol (LDL-C) but also high-density lipoprotein-cholesterol (HDL-C) levels. The latter may reduce the clinical efficacy of lomitapide. We investigated the effect of lomitapide on HDL-C levels and on cholesterol efflux capacity (CEC) of HDL in patients with homozygous familial hypercholesterolemia (HoFH). Methods and results Four HoFH patients were treated with increasing dosages of lomitapide. Lomitapide decreased LDL-C (range −34 to −89%). Total HDL-C levels decreased (range −16 to −34%) with a shift to buoyant HDL. ABCA1-mediated CEC decreased in all patients (range −39 to −99%). The changes of total, ABCG1- and SR-BI-me…
Effect of single-dose and short-term administration of quercetin on the pharmacokinetics of talinolol in humans – Implications for the evaluation of …
2013
Quercetin has been shown to inhibit intestinal P-glycoprotein-mediated drug efflux. A crossover clinical study was performed in 10 healthy volunteers to assess the effect of single-dose and repeated quercetin intake on the pharmacokinetics of talinolol, a substrate of intestinal P-glycoprotein. Unexpectedly, mean area under the plasma concentration-time curve (AUC0-48h) and maximal plasma concentration (cmax) were slightly decreased following concomitant and short-term quercetin administration (3186.0 versus 2468.3 and 2527.7 ng h/ml, p>0.05; 309.7 versus 212.0 and 280.6 ng/ml, p>0.05). Individual analysis revealed that talinolol AUC0-48h was lowered by 23.9% up to 60.6% in 5 subjects and c…
Effect of ouabain and furosemide on erythrocyte sodium and phosphate transport.
1981
The effects of ouabain and furosemide on the unidirectional efflux of sodium and phosphate ions were studied in freshly drawn human red blood cells (RBCs). In the presence of physiologic concentrations of sodium and potassium the rate of sodium efflux was reduced by 74% due to ouabain sensitivity. Furosemide (1.0 mmol/l) reduced ouabain-insensitive sodium transport rate by a further 50%. Thus, 13% of total sodium efflux was inhibited by furosemide when ouabain was present. In the absence of ouabain, however, furosemide inhibited 31% of total sodium transport, indicating that it also affected ouabain-sensitive sodium efflux. Phosphate transfer of RBCs was almost 1.0 mmol/l RBCs per hour. Ery…
Plasma and fibroblasts of Tangier disease patients are disturbed in transferring phospholipids onto apolipoprotein A-I
1998
Plasmas of patients with Tangier disease (TD) lack lipid-rich α-HDL which, in normal plasma, constitutes the majority of high density lipoprotein (HDL). Residual amounts of apolipoprotein (apo)A-I in TD plasma occur as lipid-poor or even lipid-free preβ-HDL. By contrast to normal plasma, TD plasma does not convert preβ-HDL into α-HDL. Moreover, fibroblasts of TD patients were found to be defective in secreting cholesterol or phospholipids in the presence of lipid-free apoA-I. We have therefore hypothesized that both defective conversion of preβ-HDL into α-HDL and defective lipid efflux from TD cells onto lipid-free apoA-I result from a disturbance in phospholipid transfer occurring in both …
C4-dicarboxylate carriers and sensors in bacteria
2002
AbstractBacteria contain secondary carriers for the uptake, exchange or efflux of C4-dicarboxylates. In aerobic bacteria, dicarboxylate transport (Dct)A carriers catalyze uptake of C4-dicarboxylates in a H+- or Na+-C4-dicarboxylate symport. Carriers of the dicarboxylate uptake (Dcu)AB family are used for electroneutral fumarate:succinate antiport which is required in anaerobic fumarate respiration. The DcuC carriers apparently function in succinate efflux during fermentation. The tripartite ATP-independent periplasmic (TRAP) transporter carriers are secondary uptake carriers requiring a periplasmic solute binding protein. For heterologous exchange of C4-dicarboxylates with other carboxylic …
Sometimes less is more—the impact of the number of His residues on the stability of Zn(ii)–SmtB and BigR4 α-5 domain complexes
2021
The increasing number of antibiotic-resistant pathogens has become one of the major health problems of modern times, including infections caused by Mycobacterium tuberculosis. One of the possible mammalian immune system responses to mycobacterial infection is the increase of the zinc(II) concentration in phagosomes to a toxic level. The mycobacterial SmtB protein belongs to the family of ArsR/SmtB transcription regulators. In the presence of high concentrations of metals, SmtB dissociates from DNA and activates the expression of metal efflux proteins. In this work, we focus on the α5 zinc(II) binding domains of SmtB/BigR4 proteins (the latter being the SmtB homolog from non-pathogenic M. sm…
Bacterial metal nanoparticles to develop new weapons against bacterial biofilms and infections
2021
The widespread use of antibiotics has resulted in the outbreak and spread of antibiotic-resistant pathogens. Bacterial antibiotic resistance may develop at cellular and community levels. In the latter case, it is based on tolerance which implicates the shift from a free-living form of life (i.e., planktonic) to a sessile multi-stratified community (i.e., biofilm). Metal nanoparticles (MNPs) have been shown to be promising candidates as antimicrobial agents. MNPs are able to interact with and penetrate bacterial biofilms, thus, resulting effective antibiofilm compounds. Another interesting aspect is the possibility of using plants, fungi, yeasts, and bacteria to obtain biogenic MNPs (BMNP). …
DctA- and Dcu-independent transport of succinate in Escherichia coli : contribution of diffusion and of alternative carriers
2001
Quintuple mutants of Escherichia coli deficient in the C4-dicarboxylate carriers of aerobic and anaerobic metabolism (DctA, DcuA, DcuB, DcuC, and the DcuC homolog DcuD, or the citrate/succinate antiporter CitT) showed only poor growth on succinate (or other C4-dicarboxylates) under oxic conditions. At acidic pH (pH 6) the mutants regained aerobic growth on succinate, but not on fumarate. Succinate uptake by the mutants could not be saturated at physiological succinate concentrations (≤5 mM), in contrast to the wild-type, which had a K m for succinate of 50 µM and a V max of 35 U/g dry weight at pH 6. At high substrate concentrations, the mutants showed transport activities (32 U/g dry weigh…
Modulation of P-Glycoprotein-Mediated Multidrug Resistance by Synthetic and Phytochemical Small Molecules, Monoclonal Antibodies, and Therapeutic Nuc…
2014
Multidrug resistance of malignant tumors severely hampers their successful treatment frequently leading to fatal consequences for affected patients. During the past three decades, many efforts have been spent to develop strategies to overcome multidrug resistance. Many chemical compounds have been shown to inhibit the drug efflux of the multidrug-resistance-mediating P-glycoprotein. Chemical P-glycoprotein inhibitors are from the classes of calcium channel antagonists, calmodulin inhibitors, cyclosporins, antiarrhythmics, hormones, antimalarials, antibiotics, detergents, beta-blockers, antidepressants, blood pressure lowering indol alkaloids, aerobic glycolysis inhibitors, HIV-protease inhi…
Clathrin-mediated constitutive endocytosis of PIN auxin efflux carriers in Arabidopsis.
2007
SummaryEndocytosis is an essential process by which eukaryotic cells internalize exogenous material or regulate signaling at the cell surface [1]. Different endocytic pathways are well established in yeast and animals; prominent among them is clathrin-dependent endocytosis [2, 3]. In plants, endocytosis is poorly defined, and no molecular mechanism for cargo internalization has been demonstrated so far [4, 5], although the internalization of receptor-ligand complexes at the plant plasma membrane has recently been shown [6]. Here we demonstrate by means of a green-to-red photoconvertible fluorescent reporter, EosFP [7], the constitutive endocytosis of PIN auxin efflux carriers [8] and their …