Showing papers on "Serum albumin published in 2008"
TL;DR: This review brings together recent insights on albumin antioxidant properties and describes the role of albumin in ligand binding and free radical‐trapping activities, concerning protein antioxidation.
925 citations
TL;DR: In diabetic hemodialysis patients, hemoglobin A(1c) levels significantly underestimate glycemic control while those of glycated albumin more accurately reflect this control.
307 citations
TL;DR: The results provide the first crystal structure of a natural bilirubin pigment bound to serum albumin, challenge some of the present conceptions about HSA–bilirubsin interactions, and provide a sound structural framework for finally resolving the long-standing question of where 4Z,15Z-bilirUBin-IXα binds to the protein.
235 citations
TL;DR: Comparisons of X-ray crystal structures of free and fatty-acid bound human serum albumin suggest that zinc binding to this site and fatty acid binding to one of the five major sites may be interdependent, and interactive binding of zinc and long-chain fatty acids to albumin may have physiological implications.
Abstract: Although details of the molecular mechanisms for the uptake of the essential nutrient zinc into the bloodstream and its subsequent delivery to zinc-requiring organs and cells are poorly understood, it is clear that in vertebrates the majority of plasma zinc (9–14 μM; approx. 75–85%) is bound to serum albumin, constituting part of the so-called exchangeable pool. The binding of metal ions to serum albumins has been the subject of decades of studies, employing a multitude of techniques, but only recently has the identity and putative structure of the major zinc site on albumin been reported. Intriguingly, this site is located at the interface between two domains, and involves two residues from each of domains I and II. Comparisons of X-ray crystal structures of free and fatty-acid bound human serum albumin suggest that zinc binding to this site and fatty acid binding to one of the five major sites may be interdependent. Interactive binding of zinc and long-chain fatty acids to albumin may therefore have physiological implications.
234 citations
TL;DR: It could be shown that the kinetics of particle degradation was dependent on the degree of particle stabilisation, which will influence drug release after cellular accumulation of HSA nanoparticles.
208 citations
TL;DR: The development of a novel serum albumin binding protein showing an extremely high affinity (K(D)) for HSA in the femtomolar range is described and a capture experiment involving human serum indicated that the selectivity for serumalbumin had not been compromised from the affinity engineering.
Abstract: We describe the development of a novel serum albumin binding protein showing an extremely high affinity (K(D)) for HSA in the femtomolar range. Using a naturally occurring 46-residue three-helix bundle albumin binding domain (ABD) of nanomolar affinity for HSA as template, 15 residues were targeted for a combinatorial protein engineering strategy to identify variants showing improved HSA affinities. Sequencing of 55 unique phage display-selected clones showed a strong bias for wild-type residues at nine positions, whereas various changes were observed at other positions, including charge shifts. Additionally, a few non-designed substitutions appeared. On the basis of the sequences of 12 variants showing high overall binding affinities and slow dissociation rate kinetics, a set of seven 'second generation' variants were constructed. One variant denoted ABD035 displaying wild-type-like secondary structure content and excellent thermal denaturation/renaturation properties showed an apparent affinity for HSA in the range of 50-500 fM, corresponding to several orders of magnitude improvement compared with the wild-type domain. The ABD035 variant also showed an improved affinity toward serum albumin from a number of other species, and a capture experiment involving human serum indicated that the selectivity for serum albumin had not been compromised from the affinity engineering.
200 citations
TL;DR: Molecular docking showed that the MTX binds HSA to a non-classical drug binding site and synchronous fluorescence, thermodynamic parameters and molecular modeling, which entails that hydrophobic interactions, hydrogen bonding and electrostatic forces, stabilizes the interaction.
182 citations
TL;DR: It is concluded that BSA and HSAFAF reduce the Km values of only those enzymes inhibited by long-chain unsaturated fatty acids.
Abstract: Bovine serum albumin (BSA) and fatty acid-free human serum albumin (HSAFAF) reduce the K(m) values for UGT2B7 substrates by sequestering inhibitory long-chain fatty acids released by incubations of human liver microsomes (HLM) and HEK293 cells expressing this enzyme. However, the scope of the "albumin effect" is unknown. In this investigation we characterized the effects of albumin on the kinetics of 4-methylumbelliferone (4MU) glucuronidation by UDP-glucuronosyltransferase (UGT) 1A1, 1A6, and 1A9, and propofol (PRO) glucuronidation by UGT1A9 and HLM. BSA and HSAFAF, but not human serum albumin, reduced the K(m) values for 4MU and PRO glucuronidation by UGT1A9. For example, HSAFAF (2%) reduced the K(m) values for 4MU and PRO glucuronidation from 13.4 to 2.9 and 41 to 7.2 microM, respectively. Similarly, HSAFAF (2%) reduced the K(m) for PRO glucuronidation by HLM from 127 to 10.6 muM. Arachidonic, linoleic, and oleic acids and a mixture of these decreased the rates of 4MU and PRO glucuronidation by UGT1A9. K(m) values for these reactions were increased 3- to 6-fold by the fatty acid mixture. Inhibition was reversed by the addition of BSA (2%). Extrapolation of kinetic constants for PRO glucuronidation by HLM in the presence of HSAFAF predicted in vivo hepatic clearance within 15%. Fatty acids had no effect on 4MU glucuronidation by UGT1A1 and UGT1A6 but, paradoxically, all forms of albumin altered the kinetic model for 4MU glucuronidation by UGT1A6 (from Michaelis-Menten to two-site). Only BSA caused a similar effect on 4MU glucuronidation by UGT1A1. It is concluded that BSA and HSAFAF reduce the K(m) values of only those enzymes inhibited by long-chain unsaturated fatty acids.
159 citations
TL;DR: This is the first study demonstrating a specific trastuzumab-based targeting of HER2 overexpressing breast cancer cells with doxorubicin-loaded nanoparticles, and the results indicate that these cell-type specific drug- loaded nanoparticles could achieve an improvement in cancer therapy.
137 citations
TL;DR: It was shown that the charge effect and the shape memory effect were the major factors affecting the imprint formation and template recognition of the stimuli-responsive protein imprinted polymer.
Abstract: A novel stimuli-responsive protein imprinted polymer for selective recognition of bovine serum albumin is presented. N-[3-(Dimethylamino)propyl]-methacrylamide, which is positively charged in neutral solution and is able to self-assemble onto the template protein through electrostatic interaction, was chosen as the functional monomer. Polymerization was carried out in the presence of N-isopropylacrylamide as an assistant monomer, which resulted in a stimuli-responsive protein imprinted polymer. The template proteins were easily removed by treatment with 500 mmol L(-1) NaCl solution. The influences of the external stimuli, such as temperature and ionic strength, on the polymer affinity were investigated, and a clear conformational memory was observed. The association constant ( Ka) and binding capacity ( Qmax) for the specific interaction between the protein imprinted polymer and the template protein were determined by Scatchard plots and found to be 9.6 x 10(4) L mol(-1) and 4.7 micromol g(-1), respectively. Several proteins different in molecular weight and isoelectric point were employed as reference, and it was shown that the charge effect and the shape memory effect were the major factors affecting the imprint formation and template recognition. Finally, this imprinted polymer was used to purify the bovine serum albumin from the protein mixture and real sample, which demonstrated its high selectivity.
135 citations
TL;DR: Compared with SF solution, SF-BSA-NP showed a much higher drug distribution into liver and a lower drug concentration in other tissues, after intravenously injected to mice, suggesting it might be a suitable controlled released carrier for the freely water-soluble drug SF and further hepatic targeted drug delivery.
TL;DR: Fluorescence properties of albumin were altered by oxidation and, in patients with acute-on-chronic liver failure, by high plasma levels of bilirubin, providing evidence for a preferred binding of bilIRubin to the fully reduced form ofalbumin.
TL;DR: It was concluded that colchicine may probably cause displacement of phenylbutazone from its complex with serum albumin (SA) and Static and dynamic quenching for the binary and ternary systems showed that phenyl butazone does not affect the complex formed between colchichine and BSA, and colchicaine has no effect on the Phe–BSA complex.
TL;DR: In this study, an aqueous solution of 13-nm gold nanoparticles covalently bonded with human serum albumin (HSA) was used for sensing lysozyme (Lys) and it was found that the sensitivity of HSA-AuNPs for Lys was highly dependent on the HSA concentration.
Abstract: In this study, an aqueous solution of 13-nm gold nanoparticles (AuNPs) covalently bonded with human serum albumin (HSA) was used for sensing lysozyme (Lys). HSA molecules were good stabilizing agents for AuNPs in high-salt solution and exhibited the ability to bond with Lys electrostatically. The aggregation of HSA-AuNPs was achieved upon the addition of high-pI proteins, such as Lys, α-chymotrypsinogen A, and conalbumin. Not the same was achieved, however, when low-pI proteins such as ovalbumin, bovine serum albumin, and α-lactalbumin were added. Matrix-assisted desorption/ionization mass spectrometry was used to demonstrate the interaction between HSA-AuNPs and Lys. It was found that the sensitivity of HSA-AuNPs for Lys was highly dependent on the HSA concentration. The Lys-induced aggregation of HSA-AuNPs was suggested based on the London−van der Waals attractive force. We further improved the selectivity of the probe by adjusting the pH solution to 8.0. Under the optimum conditions, the selectivity of...
TL;DR: Serum glycated albumin may offer a better index for monitoring glycemic control in pregnancy thanks to a negative correlation with MCH, serum transferrin saturation, and serum ferritin.
Abstract: OBJECTIVE —A1C levels have been shown to be elevated in relation to glycemia in late pregnancy, although the precise mechanisms remain undetermined. We hypothesized that iron deficiency is involved in the A1C increase in late pregnancy. RESEARCH DESIGN AND METHODS —In study 1, A1C, serum glycated albumin, erythrocyte indexes, and iron metabolism indexes were determined in 47 nondiabetic pregnant women not receiving iron supplementation who were divided into four groups according to gestational period (group I, 21–24 weeks; group II, 25–28 weeks; group III, 29–32 weeks; and group IV, 33–36 weeks). In study 2, these determinants were obtained at two gestational periods (20–23 weeks and 32–33 weeks) in 17 nondiabetic pregnant women. RESULTS —In study 1, A1C levels were higher in groups III and IV than those in groups I and II, whereas serum glycated albumin levels were not different among these four groups. Hemoglobin, mean corpuscular hemoglobin (MCH), serum transferrin saturation, and serum ferritin were lower in groups III and IV. A1C levels were negatively correlated with MCH, serum transferrin saturation, and serum ferritin. In study 2, A1C levels were significantly increased at gestational weeks 32–33 from those at weeks 20–23, whereas serum glycated albumin levels did not differ between the two gestational periods. MCH, serum transferrin saturation, and serum ferritin were decreased at gestational weeks 32–33. A1C levels showed a negative correlation with MCH, serum transferrin saturation, and serum ferritin. CONCLUSIONS —A1C levels were elevated in late pregnancy owing to iron deficiency. Serum glycated albumin may offer a better index for monitoring glycemic control in pregnancy.
Abstract: IL-6 regulates the synthesis of a broad spectrum of acute phase proteins in the liver. Also, it is involved in the pathogenesis of many fibrogenic diseases. To study the inflammatory effects of IL-6 on the liver in vivo, human rIL-6, produced in Escherichia coli, was injected intraperitoneally into rats (25 micrograms/100 g body weight). The major fraction of injected IL-6 was accumulated in the liver within 40 min, and the number of platelets was increased during 72 h after injection. After 5 weeks of injection, the levels of serum glutamine pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase (GOT) were not changed, but they were significantly elevated at 13 weeks of treatment. Meanwhile, serum albumin levels were slightly decreased compared with those of controls. The same phenomena were observed in carbon tetrachloride-treated rats. Collagen synthesis was increased in the liver tissues and in the culture supernatants of hepatic lipocytes isolated from the rats treated with IL-6 for 13 weeks. Histological analysis correlated well with biochemical analysis. At 5 weeks of treatment, only mild pathological changes were observed, but severe hepatocyte necrosis and the accumulation of fibres in necrotic area were developed in the liver of IL-6-treated rats after 13 weeks of treatment, confirming that hepatic inflammation and fibrosis were developed. IL-6 activities in the sera and in the culture supernatants of lipocytes from IL-6-treated rats were elevated compared with those in controls. These biochemical and pathological data indicate that IL-6 can induce hepatic inflammation, and it has important roles in the pathogenesis of fibrosis and diseases of the liver in vivo. In addition, these results will provide useful information for the clinical trials of IL-6.
Journal Article•
TL;DR: In this paper, the authors proposed using the in vitro anti-denaturation (stabilization) effects of heat treated (immunogenic) bovine serum albumin (BSA) as an assay.
Abstract: There are emerging ethical issues with regards to the use of animals in the early stages of drug discovery for anti-inflammatory and degenerative diseases from natural products using the activity-directed isolation pathways when many compounds (eg > 100) are present in the crude extract or fraction and are to be tested The above-mentioned is the main reason for proposing the use of the in vitro anti-denaturation (stabilization) effects of heat treated (immunogenic) bovine serum albumin (BSA) as an assay. Current methods used for detecting and isolating a wide range of anti-inflammatory compounds in the early stages of the drug discovery process utilize a large number of animals. When BSA is heated and is undergoing denaturation, it expresses antigens associated to Type III hypersensitive reaction and which are related to diseases such as serum sickness, glomerulonephritis, rheumatoid arthritis and systemic lupus erythematosus. Thus, the assay that is being proposed should be applicable to the discovery of drugs for treating the above mentioned diseases and others, once the compounds stabilize the denaturation process.
TL;DR: The pseudo-esterase activity of albumin is the result of irreversible acetylation of 82 residues and is notThe result of turnover.
TL;DR: The synthesis and testing of a new synthetic plasma expander that can replace not only the osmotic and volume expansion properties of HSA but, uniquely, its binding and transport properties is reported here.
TL;DR: Free, unbound antibiotic concentrations differed substantially between plasma and protein supplements and correlated well with antimicrobial efficacy, therefore, free, active concentrations should be measured in the test system instead of correcting for literature protein binding values.
Abstract: During antibiotic drug development, media are frequently spiked with either serum/plasma or protein supplements to evaluate the effect of protein binding Usually, previously reported serum or plasma protein binding values are applied in the analysis The aim of this study was to evaluate this approach by experimentally measuring free, unbound concentrations for antibiotics with reportedly high protein binding and their corresponding antimicrobial activities in media containing commonly used protein supplements Free, unbound ceftriaxone and ertapenem concentrations were determined in bacterial growth medium with and without bovine/human serum albumin, as well as adult bovine serum and human plasma using in vitro microdialysis The corresponding antimicrobial activity was determined in MIC and time-kill curve experiments using Escherichia coli ATCC 25922 and Streptococcus pneumoniae ATCC 6303 as test strains A semimechanistic maximum effect model was simultaneously fitted to the data and respective EC(50) (concentration at half-maximum effect) values compared Protein binding differed significantly for ceftriaxone (P < 005) between human plasma (768 +/- 110%) and commercially available bovine (202 +/- 83%) or human serum albumin (569 +/- 166%) Similar results were obtained for ertapenem (human plasma, 738 +/- 116%; bovine serum albumin, 124 +/- 48%; human serum albumin, 178 +/- 115%) The MICs and EC(50)s of both strains were significantly increased (P < 005) for ceftriaxone when comparing human and bovine serum albumin, whereas the EC(50)s were not significantly different for ertapenem Free, unbound antibiotic concentrations differed substantially between plasma and protein supplements and correlated well with antimicrobial efficacy Therefore, free, active concentrations should be measured in the test system instead of correcting for literature protein binding values
TL;DR: A micro pH sensor obtained from the BSA fiber stained with a fluorescein derivative (FITC) is shown, which can be easily modified to be used as two-dimensional biosensors.
TL;DR: Though the concentration of albumin in plasma is very high, its reactivity with soman (phosphonylation and phosphotriesterase activity) is too slow to play a major role in detoxification of the highly toxic organophosphorus compound soman.
Abstract: Human plasma and fatty acid free human albumin were incubated with soman at pH 8.0 and 25 degrees C. Four methods were used to monitor the reaction of albumin with soman: progressive inhibition of the aryl acylamidase activity of albumin, the release of fluoride ion from soman, 31P NMR, and mass spectrometry. Inhibition (phosphonylation) was slow with a bimolecular rate constant of 15 +/- 3 M(-1) min (-1). MALDI-TOF and tandem mass spectrometry of the soman-albumin adduct showed that albumin was phosphonylated on tyrosine 411. No secondary dealkylation of the adduct (aging) occurred. Covalent docking simulations and 31P NMR experiments showed that albumin has no enantiomeric preference for the four stereoisomers of soman. Spontaneous reactivation at pH 8.0 and 25 degrees C, measured as regaining of aryl acylamidase activity and decrease of covalent adduct (pinacolyl methylphosphonylated albumin) by NMR, occurred at a rate of 0.0044 h (-1), indicating that the adduct is quite stable ( t1/2 = 6.5 days). At pH 7.4 and 22 degrees C, the covalent soman-albumin adduct, measured by MALDI-TOF mass spectrometry, was more stable ( t1/2 = 20 days). Though the concentration of albumin in plasma is very high (about 0.6 mM), its reactivity with soman (phosphonylation and phosphotriesterase activity) is too slow to play a major role in detoxification of the highly toxic organophosphorus compound soman. Increasing the bimolecular rate constant of albumin for organophosphates is a protein engineering challenge that could lead to a new class of bioscavengers to be used against poisoning by nerve agents. Soman-albumin adducts detected by mass spectrometry could be useful for the diagnosis of soman exposure.
TL;DR: During brain development the presence of albumin could play an important role by triggering the synthesis and release of oleic acid by astrocytes, which induces neuronal differentiation.
Abstract: Unlike in the adult brain, the newborn brain specifically takes up serum albumin during the postnatal period, coinciding with the stage of maximal brain development. Here we report that albumin stimulates oleic acid synthesis by astrocytes from the main metabolic substrates available during brain development. Oleic acid released by astrocytes is used by neurons for the synthesis of phospholipids and is specifically incorporated into growth cones. Oleic acid promotes axonal growth, neuronal clustering, and expression of the axonal growth-associated protein-43, GAP-43; all these observations indicating neuronal differentiation. The effect of oleic acid on GAP-43 synthesis is brought about by the activation of protein kinase C, since it was prevented by inhibitors of this kinase, such as H-7, polymyxin or sphingosine. The expression of GAP-43 was significantly increased in neurons co-cultured with astrocytes by the presence of albumin indicating that neuronal differentiation takes place in the presence of oleic acid synthesized and released by astrocytes in situ. In conclusion, during brain development the presence of albumin could play an important role by triggering the synthesis and release of oleic acid by astrocytes, which induces neuronal differentiation.
TL;DR: Different spectroscopic methods were applied to study the effects of the interaction of vanadyl and vanadate species with BSA, considered as the most abundant plasma protein.
TL;DR: Modified BSA revealed reduction of amino groups' availability and slower migration through SDS/PAGE, and only BSA-lactose showed biological recognition by specific lectins.
Abstract: The non-enzymatic reaction between reducing sugars and proteins, known as glycation, has received increased attention from nutritional and medical research. In addition, there is a large interest in obtaining glycoconjugates of pure well-characterized oligosaccharides for biological research. In this study, glycation of bovine serum albumin (BSA) by d-glucose, d-galactose and d-lactose under dry-heat at 60 degrees C for 30, 60, 120, 180 or 240 min was assessed and the glycated products studied in order to establish their biological recognition by lectins. BSA glycation was monitored using gel electrophoresis, determination of available amino groups and lectin binding assays. The BSA molecular mass increase and glycation sites were investigated by mass spectrometry and through digestion with trypsin and chymotrypsin. Depending on time and type of sugar, differences in BSA conjugation were achieved. Modified BSA revealed reduction of amino groups' availability and slower migration through SDS/PAGE. d-galactose was more reactive than d-glucose or d-lactose, leading to the coupling of 10, 3 and 1 sugar residues, respectively, after 120 minutes of reaction. BSA lysines (K) were the preferred modified amino acids; both K256 and K420 appeared the most available for conjugation. Only BSA-lactose showed biological recognition by specific lectins.
TL;DR: Sclerosants at therapeutic concentrations lyse blood cells and endothelial cells in vitro and the effect is strongly reduced by serum albumin possibly contributing towards the low incidence of thromboembolic complications of sclerotherapy.
TL;DR: This study described a preparation procedure for BSA NPs with controllable particle size, and such polymer-coated B SA NPs are promising delivery agents for local and systemic administration of BMP-2 in bone regeneration.
Abstract: Purpose
The purpose of this study was to investigate the preparation process of bone morphogenetic protein-2 (BMP-2) containing bovine serum albumin (BSA) nanoparticles (NPs), and to assess the bioactivity of BMP-2 encapsulated in such NPs.
TL;DR: Analytical methods for measuring haptoglobin, serum amyloid A, SAA, acid soluble glycoprotein, ASG, fibrinogen, and albumin concentrations in goats were validated and their response to an inflammatory stimulus in this species was evaluated.
Abstract: Acute phase proteins (APPs) are important diagnostic indicators of inflammatory disturbances in animals. The objectives of the current study were to validate analytical methods for measuring haptoglobin (Hp), serum amyloid A (SAA), acid soluble glycoprotein (ASG), fibrinogen, and albumin concentrations in goats and to evaluate their response to an inflammatory stimulus in this species. Intra- and interassay coefficients of variation (CVs) were in the range 0.07-9.31% and 1.83-12.68%, respectively, for all APPs and showed good precision. All assays determined APPs in a linear manner at different sample dilutions with high correlation coefficients with the exception of fibrinogen, which was measured by the heat precipitation method. Subcutaneous injection of turpentine oil induced an increase in Hp, SAA, ASG, and fibrinogen serum concentrations and a decrease in albumin concentration.
TL;DR: The helicity of the (SSS)-Delta enantiomer of a terbium and europium(III) complex is inverted on reversible binding to 'drug site II' of serum albumin, signalled by a switch in its circularly polarised emission; no such behaviour occurs with the (RRR)-Lambda complexes, thereby defining a unique chiroptical probe of albumin binding.
TL;DR: It is concluded that heating reduces sensitization to beef and bovine serum albumin but does not abolish reactivity to albumin under home conditions, however, industrially heat‐treated and sterilized homogenized beef and freeze‐dried beef may be suitable substitutes in beef‐allergic children's diets.
Abstract: The effect of heat on the allergenicity of beef and bovine serum albumin was investigated among 10 toddlers skin prick test (SPT)-positive to raw and cooked beef. The meat-allergy diagnosis was confirmed during double-blind, placebo-controlled food challenge (DBPCFC) with 180 g of beef cooked for 5 min at 100 degrees C. SPT with homogenized and freeze-dried beef, and heated and unheated bovine serum albumin were performed. Both heated and unheated bovine serum albumin, homogenized beef, and freeze-dried beef were used in trial DBPCFC. All children were SPT-positive to unheated bovine serum albumin. Seven were positive to heated bovine serum albumin, one to freeze-dried beef, and none to homogenized beef. DBPCFCs were negative for homogenized beef and freeze-dried beef, positive for unheated bovine serum albumin in five patients, and positive for heated albumin in four children. We conclude that heating reduces sensitization to beef and bovine serum albumin but does not abolish reactivity to albumin under home conditions. However, industrially heat-treated and sterilized homogenized beef and freeze-dried beef may be suitable substitutes in beef-allergic children's diets.