Showing papers on "Human serum albumin published in 2010"
TL;DR: This review aims to highlight current overview on the binding strategies of protein to various ligands that may be expected to lead to significant clinical applications.
290 citations
TL;DR: An analysis of the features of albumin leads to a consideration of the extracellular and intracellular actions of the molecule, and the role of its interactions with numerous ligands or bioactive factors that influence the growth of cells in culture.
Abstract: Albumin has a long historical involvement in design of media for the successful culture of mammalian cells, in both the research and commercial fields. The potential application of albumins, bovine or human serum albumin, for cell culture is a by-product of the physico-chemical, biochemical and cell-specific properties of the molecule. In this review an analysis of these features of albumin leads to a consideration of the extracellular and intracellular actions of the molecule, and importantly the role of its interactions with numerous ligands or bioactive factors that influence the growth of cells in culture: these include hormones, growth factors, lipids, amino acids, metal ions, reactive oxygen and nitrogen species to name a few. The interaction of albumin with the cell in relation to these co-factors has a potential impact on metabolic and biosynthetic activity, cell proliferation and survival. Application of this knowledge to improve the performance in manufacturing biotechnology and in the emerging uses of cell culture for tissue engineering and stem cell derived therapies is an important prospect.
265 citations
TL;DR: The binding affinity of human serum albumin to three antimalarial indolone-N-oxide derivatives, INODs, was investigated under simulated physiological conditions using fluorescence spectroscopy in combination with UV-vis absorption and circular dichroismSpectroscopy.
243 citations
TL;DR: It was proved that the fluorescence quenching of HSA by palmatine is a result of the formation ofPalmatine/HSA complex and the electrostatic interactions play a major role for palmatin-HSA association.
241 citations
TL;DR: A new and simple method utilizing two AuNP-antibody conjugates was developed, which was successfully applied in the analysis of serum samples of patients with myocardial infarction, and could detect as low as 0.01 ng/mL troponin I in 10 min using the dual AuNP conjugate-based LFA.
232 citations
TL;DR: It is confirmed that the protein concentration plays an important role on the pH-unfolded BSA state, due to a delicate compromise between interaction forces and crowding effects.
230 citations
TL;DR: Spectroscopic analysis of the emissionQuenching at different temperatures revealed that the quenching mechanism of serum albumin by dexamethasone is static quench mechanism.
Abstract: This study was designed to examine the interaction of dexamethasone (DEX) with bovine serum albumin (BSA) and human serum albumin (HSA) under physiological conditions with drug concentrations in the range of 2.5-20 microM and BSA/HSA was fixed at 5.0 microM. Spectroscopic analysis of the emission quenching at different temperatures revealed that the quenching mechanism of serum albumin by dexamethasone is static quenching mechanism. The binding sites number, n and binding constant, K were obtained at various temperatures. The distance r between dexamethasone and the protein was evaluated according to the theory of Foster energy transfer. The result of fluorescence spectra UV-vis absorption spectra and FT-IR spectra showed that the conformation of bovine serum albumin and human serum albumin has been changed in the presence of dexamethasone. The thermodynamic parameters, free energy change (DeltaG(0)), enthalpy change (DeltaH(0)) and entropy change (DeltaS(0)) for BSA-DEX and HSA-DEX were calculated according to van't Hoff equation and discussed.
202 citations
TL;DR: The interactions of 3-carboxyphenoxathiin with BSA and HSA have been studied by fluorescence and circular dichroism spectroscopy, revealing a 1:1 interaction with a binding constant of about 105 M-1.
Abstract: The interactions of 3-carboxyphenoxathiin with Bovine Serum Albumin (BSA) and Human Serum Albumin (HSA) have been studied by fluorescence and circular dichroism spectroscopy. The binding of 3-carboxyphenoxathiin quenches the BSA and HSA fluorescence, revealing a 1:1 interaction with a binding constant of about 10(5) M(-1). In addition, according to the synchronous fluorescence spectra of BSA and HSA in presence of 3-carboxyphenoxathiin, the tryptophan residues of the proteins are most perturbed by the binding process. Finally, the distance between the acceptor, 3-carboxyphenoxathiin, and the donor, BSA or HSA, was estimated on the basis of the Forster resonance energy transfer (FRET). The fluorescence results are correlated with those obtained from the circular dichroism spectra, which reveal the change of the albumin conformation during the interaction process.
202 citations
TL;DR: A readily accessible fluorescent bioprobe for HSA detection and quantitation and Computational modeling suggests that the AIE luminogens dock in the hydrophobic cleft between subdomains IIA and IIIA of HSA with the aid of hydrophilic effect, charge neutralization, and hydrogen bonding interactions, offering mechanistic insight into the microenvironment inside theHydrophobic cavity.
Abstract: Human serum albumin (HSA) is a major protein component of blood plasma, and its assay is of obvious value to biological research. We, herein, present a readily accessible fluorescent bioprobe for HSA detection and quantitation. A nonemissive tetraphenylethene derivative named sodium 1,2-bis[4-(3-sulfonatopropoxyl)phenyl]-1,2-diphenylethene (BSPOTPE) is induced to emit by HSA, showing a novel phenomenon of aggregation-induced emission (AIE). The AIE bioprobe enjoys a broad working range (0−100 nM), a low detection limit (down to 1 nM), and a superior selectivity to albumins. The fluorescent bioassay is unperturbed by the miscellaneous bioelectrolytes in the artificial urine. The AIE luminogen can also be used as a rapid and sensitive protein stain in gel electrophoresis for HSA visualization. Utilizing the AIE feature of BSPOTPE and the Forster resonance energy transfer from HSA to BSPOTPE, the unfolding process of HSA induced by guanidine hydrochloride is monitored, which reveals a multistep transition wi...
201 citations
TL;DR: It is concluded that vanadium compounds are mainly transported in blood by transferrin, but that no study has properly addressed the influence of albumin and transferrin in the vanadium uptake by cells.
Abstract: Low molecular weight and high molecular weight metal ion binders present in blood plasma are shortly described. The binding of vanadium and ruthenium complexes by these components has received much attention, namely their interactions with human serum albumin and transferrin, and these studies are critically reviewed. The influence of the protein binding on the bioavailability of the prospective drugs, namely on the transport by blood plasma and uptake by cells is also discussed. It is concluded that vanadium compounds are mainly transported in blood by transferrin, but that no study has properly addressed the influence of albumin and transferrin in the vanadium uptake by cells. Ruthenium complexes bind strongly to HSA, most likely at the level of His residues, leading to the formation of stable adducts. If the kinetics of binding to this protein is fast enough, probably they are mainly transported by this serum protein. Nevertheless, at least for a few Ru III -complexes, hTf seems to play an active role in the uptake of ruthenium, while HSA may provide selectivity and higher activity for the compounds due to an enhanced permeability effect.
179 citations
TL;DR: Binding studies were performed in vitro using enzyme-linked immunosorbent assay and surface plasmon resonance with recombinant soluble forms of human and mouse FcRn receptors to address cross-species ligand reactivity with F cRn.
TL;DR: Alternative ways to measure drug‐albumin interaction are examined, including fluorescence spectroscopy, which is insensitive to higher‐affinity compounds and can be labour‐intensive, time‐consuming, and usually require compound‐specific assays.
Abstract: Binding of new chemical entities to serum proteins is an issue confronting pharmaceutical companies during development of potential therapeutic agents. Most drugs bind to the most abundant plasma protein, human serum albumin (HSA), at two major binding sites. Excepting fluorescence spectroscopy, existing methods for assaying drug binding to serum albumin are insensitive to higher-affinity compounds and can be labour-intensive, time-consuming, and usually require compound-specific assays. This led us to examine alternative ways to measure drug-albumin interaction. One method described here uses fluorescence quenching of the single tryptophan (Trp) residue in HSA excited at 295 nm to measure drug-binding affinity. Unfortunately, many compounds absorb, fluoresce, or both, in this UV wavelength region of the spectrum. Several types of binding phenomenon and spectral interference were identified by use of six structurally unrelated compounds and the equations necessary to make corrections mathematically were derived and applied to calculate binding constants accurately. The general cases were: direct quenching of Trp fluorescence by optically transparent ligands with low or high affinities; binding of optically transparent, non-fluorescent ligands to two specific sites where both sites or only one site result in Trp fluorescence quenching; and chromophores whose absorption either overlaps the Trp emission and quenches by energy transfer or absorbs light at the Trp fluorescence excitation wavelength producing absorptive screening as well as fluorescence quenching. Unless identification of the site specificity of drug binding to serum albumin is desired, quenching of the Trp fluorescence of albumin by titration with ligand is a rapid and facile method for determining the binding affinities of drugs for serum albumin.
TL;DR: The interaction of kaempferol (kaemp), a natural flavonoid to which antioxidative, anti-inflammatory and cardio-protective biological activities have been attributed, with human serum albumin (HSA), the main in vivo transporter of exogenous substances, was investigated by steady-state, synchronous fluorescence and circular dichroism spectroscopies.
TL;DR: Data confirm the key role of ruthenium itself in anti-metastatic activity and the activity of osmium arene complexes in other tumour models and the possibility of changing the non-arene ligands to tune the anticancer activity of Osmium in vivo.
TL;DR: Both functional and structural aspects of the allosteric modulation of heme and drug binding to HSA and of the drug-dependent reactivity of HSA-heme are reviewed.
TL;DR: DI17E6-coupled human serum albumin nanoparticles represent a potential delivery system for targeted drug transport into alphavbeta3-positive cells and showed increased cytotoxic activity inAlphav beta3- positive melanoma cells than the free drug.
TL;DR: The molecular dynamics study makes an important contribution to understanding the effect of the binding of beta-sitosterol on conformational changes of HSA and the stability of a protein-drug complex system in aqueous solution.
Abstract: Beta-sitosterol is a naturally occurring phytosterol that is widely used to cure atherosclerosis, diabetes, cancer, and inflammation and is also an antioxidant. Here, we studied the interaction of beta-sitosterol, isolated from the aerial roots of Ficus bengalensis, with human serum albumin (HSA) at physiological pH 7.2 by using fluorescence, circular dichroism (CD), molecular docking, and molecular dynamics simulation methods. The experimental results show that the intrinsic fluorescence of HSA is quenched by addition of beta-sitosterol through a static quenching mechanism. The binding constant of the compound to HSA, calculated from fluorescence data, was found to be K(beta-sitosterol) = 4.6 +/- 0.01 x 10(3) M(-1), which corresponds to -5.0 kcal M(-1) of free energy. Upon binding of beta-sitosterol to HSA, the protein secondary structure was partially unfolded. Specifically, the molecular dynamics study makes an important contribution to understanding the effect of the binding of beta-sitosterol on conformational changes of HSA and the stability of a protein-drug complex system in aqueous solution. Molecular docking studies revealed that the beta-sitosterol can bind in the large hydrophobic cavity of subdomain IIA, mainly by the hydrophobic interaction but also by hydrogen bond interactions between the hydroxyl (OH) group of carbon-3 of beta-sitosterol to Arg(257), Ser(287), and Ala(261) of HSA, with hydrogen bond distances of 1.9, 2.4, and 2.2 A, respectively.
TL;DR: The results reported here suggest binding through specific high affinity interactions at low PFAA:albumin mole ratios.
Abstract: Preferential distribution of long-chain perfluoroalkyl acids (PFAAs) in the liver, kidney, and blood of organisms highlights the importance of PFAA-protein interactions in PFAA tissue distribution patterns. A serum protein association constant may be a useful parameter to characterize the bioaccumulative potential and in vivo bioavailability of PFAAs. In this work, association constants (Ka) and binding stoichiometries for PFAA-albumin complexes are quantified over a wide range of PFAA:albumin mole ratios. Primary association constants for perfluorooctanoate (PFOA) or perfluorononanoate (PFNA) with the model protein bovine serum albumin (BSA) determined via equilibrium dialysis are on the order of 106 M−1 with one to three primary binding sites. PFNA was greater than 99.9% bound to BSA or human serum albumin (HSA) at a physiological PFAA:albumin mole ratio ( 4). Nanoelectrospray ionization mass spectrometry (nanoESI-MS) data ...
TL;DR: N-trans-p-coumaroyltyramine isolated from Physalis minima is a phenolic substance exhibiting many pharmacological activities like potent inhibition of acetyl cholinesterase, cell proliferation, platelet aggregation, and also antioxidant activity, which indicates the hydrophobic interactions of CT with HSA and is in well agreement with the computational calculations and molecular docking studies.
Abstract: N-trans-p-coumaroyltyramine (CT) isolated from Physalis minima is a phenolic substance exhibiting many pharmacological activities like potent inhibition of acetyl cholinesterase, cell proliferation, platelet aggregation, and also antioxidant activity. Here, we have studied the binding of CT with HSA at physiological pH 7.2 by using fluorescence, circular dichroism spectroscopy, mass spectrometry, and molecular docking methods. From the fluorescence emission studies, the number of binding sites and binding constant were calculated to be 2 and (4.5 +/- 0.01) x 10(5) M(-1), respectively. The free energy change was calculated as -7.6 kcal M(-1) at 25 degrees C, which indicates the hydrophobic interactions of CT with HSA and is in well agreement with the computational calculations and molecular docking studies. The changes in the secondary structure of HSA after its complexation with the ligand were studied with CD spectroscopy, which indicated that the protein became partially unfolded. Also, temperature did not affect the HSA-CT complexes. The binding of CT with HSA was detected as 2 molecules bound to HSA was determined using micro TOF-Q mass spectrometry. Further, molecular docking studies revealed that CT was binding at subdomain IIA with hydrophobic interactions and also by hydrogen-bond interactions between the hydroxyl (OH) group of carbon-16 and carbon-2 of CT and Arg222, Ala291, Val293, and Met298 of HSA, with hydrogen-bond distances of 2.488, 2.811, 2.678, and 2.586 A, respectively.
TL;DR: An overview of the state-of-the-art using albumin as drug carrier for specific accumulation in tumors and inflammatory cells using the advantageous properties of native albumin is given in this review.
Abstract: Importance in the field: Activated cells metabolize albumin to cover their increased need for amino acids and energy. In inflamed, diseased and malignant tissue, extravasation of macromolecules into the tissue is upregulated. Drug carriers such as albumin have been used to target specifically diseased and malignant cells, resulting in higher efficacy of treatment and reduced side effects.Areas covered in this review: Owing to its advantageous biochemical and pharmacological properties, albumin has been regarded as an interesting candidate as a drug carrier. Covalent coupling to albumin carries drugs specifically to tumors and sites of inflammation, leading to reduced side effects as long as the native structure of albumin is unchanged. In this review, the means of coupling drugs to native albumin as well as exemplary studies for the use of albumin as drug carrier are summarized and discussed.What the reader will gain: An overview of the state-of-the-art using albumin as drug carrier for specific accumulat...
TL;DR: Present data indicate a novel role of fatty acids as allosteric inhibitors of flavonoid bioavailability, and appear to be relevant in rationalizing the interference between dietary compounds, food supplements, and drugs.
TL;DR: A novel dopamine-plus-HSA (human serum albumin) approach was developed to functionalize iron oxide nanoparticles (IONPs), yielding nanoconjugates that are highly efficient in labeling various types of cell lines.
TL;DR: HSA nanoparticles with covalently bound apolipoprotein A-I (Apo A- I) as a targetor for brain capillary endothelial cells were injected intravenously into SV 129 mice and Wistar rats and the maintenance of tight junction integrity and barrier function during treatment with nanoparticles was demonstrated.
Abstract: Nanoparticles made of human serum albumin (HSA) and modified with apolipoproteins have previously been shown to transport drugs, which normally do not enter the brain, across the blood-brain barrier (BBB). However the precise mechanism by which nanoparticles with different apolipoproteins on their surface can target to the brain, as yet, has not been totally elucidated. In the present study, HSA nanoparticles with covalently bound apolipoprotein A-I (Apo A-I) as a targetor for brain capillary endothelial cells were injected intravenously into SV 129 mice and Wistar rats. The rodents were sacrificed after 15 or 30 min, and their brains were examined by transmission electron microscopy. Apo A-I nanoparticles could be found inside the endothelial cells of brain capillaries as well as within parenchymal brain tissue of both, mice and rats, whereas control particles without Apo A-I on their surface did not cross the BBB during our experiments. The maintenance of tight junction integrity and barrier function during treatment with nanoparticles was demonstrated by perfusion with a fixative containing lanthanum nitrate as an electron dense marker for the permeability of tight junctions.
TL;DR: It is imperative to assign a greater role of HSA's as a carrier molecule for many drugs to understand the interactions of H SA with Trimethoxy flavone, which will be pivotal in the design of new TMF-inspired drugs.
Abstract: Background
Human serum albumin (HSA) is the most abundant protein in blood plasma, having high affinity binding sites for several endogenous and exogenous compounds. Trimethoxy flavone (TMF) is a naturally occurring flavone isolated from Andrographis viscosula and used in the treatment of dyspepsia, influenza, malaria, respiratory functions and as an astringent and antidote for poisonous stings of some insects.
TL;DR: The redox state of albumin shows high variability and is hence a valuable tool for the investigation of reversible and irreversible modification of plasma protein.
Abstract: Albumin, the main protein in plasma, is prone to different mechanisms of oxidative modification since extracellular fluids contain only small amounts of antioxidant enzymes. The redox state of cysteine-34 of human albumin defines three fractions which allow to monitor albumin oxidation: mercaptalbumin with a free thiol group, nonmercaptalbumin1 containing a disulfide, and nonmercaptalbumin2 with a sulfinic or sulfonic acid group. These fractions can be separated by HPLC and detected with UV or fluorescence detection. The method is very rugged and only simple sample preparation is needed. It has been used to demonstrate albumin oxidation during exercise, aging, and pathologies like diabetes, liver disease, or renal disease. Problems may arise when high endogenous concentrations of bilirubin or certain drugs are present. The redox state of albumin shows high variability and is hence a valuable tool for the investigation of reversible and irreversible modification of plasma protein.
TL;DR: In this article, the binding properties on theasinesin to human serum albumin (HSA) have been studied for the first time using fluorescence spectroscopy in combination with UV-vis absorbance spectrography.
TL;DR: It is found that also albumin can participate in the transport of an insulin-enhancing compound forming a mixed species cis-VO(carrier)( 2)(HSA), when the carrier stabilizes in aqueous solution the cis-octahedral form, or the dinuclear compound (VO)(2)(d)HSA, when the carriers forms unstable complexes.
Abstract: The possible biotransformations in the blood serum of four representative insulin-enhancing vanadium compounds, [VO(6-mepic)2], cis-[VO(pic)2(H2O)], [VO(acac)2], and [VO(dhp)2], where 6-mepic, pic, acac, and dhp indicate the deprotonated forms of 6-methylpicolinic and picolinic acids, acetylacetone, and 1,2-dimethyl-3-hydroxy-4(1H)-pyridinone, were examined. In particular, the behavior of the quinary systems formed by the insulin-enhancing species, human serum apo-transferrin (hTf), human serum albumin (HSA), and lactate (lact) or citrate (citr) at physiological pH and conditions was studied. The results indicate that, besides the case in which the ligand is very weak like 6-mepic, the carrier can interact in some form with VO2+ ion until its intake into the cell. In fact with stronger ligands like pic, acac, and dhp, VO2+ is transported not only by transferrin but also as [VO(carrier)2] and as mixed species VO2+−hTF−carrier. There are two ways in which the undissociated form of a bis-chelated complex can...
TL;DR: Results obtained with equilibrium dialysis and isothermal titration calorimetry show that lidocaine binding is of a low affinity and occurs at one discrete binding site in accordance with the X-ray data, and contribute to a further characterisation of the exceptional binding properties of HSA.
TL;DR: The distance between the donor (serum albumins) and acceptor (gold nanoparticles) was obtained, which showed that HSA has more affinity towards sonochemically synthesized gold nanoparticle compared to gold nanoparticles synthesized using other methods.
TL;DR: The effects of glycated human serum albumin on human umbilical vein endothelial cells were studied to better understand the mechanisms behind hyperglycaemia and its effects on vascular tissue.
Abstract: Background Hyperglycaemia induces non-enzymatic glycation reactions in proteins which generate Amadori products and advanced glycation end- products; the latter are thought to participate in the vascular complications of diabetic patients. However, the exact mechanisms concerning the effects of glycated proteins on vascular tissue remain to be determined. Therefore, the effects of glycated human serum albumin on human umbilical vein endothelial cells were studied. Methods Reactive oxygen species production was measured by the cytochrome C reduction method and by 5(6)-carboxy-2′,7′-dichlorofluorescein diacetate (c-DCF-DA) fluorescence after treating human umbilical vein endothelial cells with glycated human serum albumin (6-200 μg/mL). The expression of Nox4 and p22phox mRNAs were analysed by reverse transcription-quantitative polymerase chain reactions and the levels of their proteins were measured by immunofluorescence. Results Low concentrations of glycated human serum albumin enhanced reactive oxygen species production in human umbilical vein endothelial cells after 4 h of treatment at both extracellular and intracellular sites. This enhanced production was sustained, although to a lesser extent, after 6 and 12 h of treatment. The gene expression study revealed that Nox4 and p22phox mRNA levels were elevated after 4 h of treatment with glycated human serum albumin. This mRNA elevation and enhanced reactive oxygen species production correlated with an increased expression of the Nox4 protein. Conclusions The results revealed that a circulating and abundant modified glycated human serum albumin protein in diabetic patients induced a sustained reactive oxygen species production in human endothelial cells. This effect may have been due to an up-regulation of Nox4, the main subunit of NADPH oxidase in the endothelium. © 2010 John Wiley & Sons, Ltd.