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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular endothelial cells undergo albumin endocytosis using a set of albumin binding proteins. This process is important for maintaining cellular homeostasis. We showed by several criteria that the previously described 73-kDa endothelial cell surface albumin binding protein is the 75-kDa transforming growth factor (TGF)-beta receptor type II (TbetaRII). Albumin coimmunoprecipitated with TbetaRII from a membrane fraction from rat lung microvascular endothelial cells. Albumin endocytosis-negative COS-7 cells became albumin endocytosis competent when transfected with wild-type TbetaRII but not when transfected with a domain-negative kinase mutant of TbetaRII. An antibody specific for TbetaRII inhibited albumin endocytosis. A mink lung epithelial cell line, which expresses both the TGF-beta receptor type I (TbetaRI) and the TbetaRII receptor, exhibited albumin binding to the cell surface and endocytosis. In contrast, mutant L-17 and DR-26 cells lacking TbetaRI or TbetaRII, respectively, each showed a dramatic reduction in binding and endocytosis. Albumin endocytosis induced Smad2 phosphorylation and Smad4 translocation as well as increased protein expression of the inhibitory Smad, Smad7. We identified regions of significant homology between amino acid sequences of albumin and TGF-beta, suggesting a structural basis for the interaction of albumin with the TGF-beta receptors and subsequent activation of TbetaRII signaling. The observed albumin-induced internalization of TbetaRII signaling may be an important mechanism in the vessel wall for controlling TGF-beta responses in endothelial cells.
Am J Physiol Lung Cell Mol Physiol 2004 May
PMID:Albumin endocytosis in endothelial cells induces TGF-beta receptor II signaling. 1472 11

Binding of chlorpromazine (CPZ) and hemin (Hmn) to human (HSA) and bovine (BSA) serum albumin was studied by fluorescence quenching technique. Intrinsic fluorescences of BSA and HSA were measured by selectively exciting their tryptophan residues. Gradual quenching was observed by titration of both proteins with CPZ and Hmn. CPZ is a widely used anti-psychosis drug that causes severe side effects and strongly interacts with biomembranes, both in its lipidic and proteic regions. CPZ also interacts with blood components, influences bioavailability, and affects the function of several biomolecules. Albumin plays an important role in the transport and storage of hormones, ions, fatty acids and others substances, including CPZ, affecting the regulation of their plasmatic concentration. Hmn is an important ferric residue of hemoglobin that binds within the hydrophobic region of albumin with great specificity. Hmn added to HSA and BSA solutions at a molar ratio of 1:1 quenched about half of their fluorescence. Stern-Volmer plots obtained from experiments carried out at 25 and 35 degrees C showed the quenching of fluorescence of HSA and BSA by CPZ to be a collisional phenomenon. Hmn quenches fluorescence by a static process, which specifically indicates the formation of a complex. Our results suggest the prime binding site for CPZ and Hmn on both HSA and BSA to be near tryptophan residues.
Spectrochim Acta A Mol Biomol Spectrosc 2004 Apr
PMID:Chlorpromazine interactions to sera albumins. A study by the quenching of fluorescence. 1508 40

Albumin has been shown to be expressed in osteoblastic cells. The role of albumin in osteoblastic cells was investigated. Osteoblastic MC3T3-E1 cells with subconfluent monolayers were cultured for 24 or 48 h in a medium without fetal bovine serum (FBS) in the presence or absence of albumin (0.5 or 1.0 mg/ml of medium) or insulin-like growth factor-I (IGF-I; 10(-9) or 10(-8) M). The number of osteoblastic cells was significantly increased by culture for 48 h in the presence of albumin (0.5 or 1.0 mg/ml) or IGF-I (10(-9) or 10(-8) M). The effect of albumin (0.5 or 1.0 mg/ml) in increasing the cell number was not significantly modulated in the presence of IGF-I (10(-9) or 10(-8) M). Protein content in osteoblastic cells was significantly increased by culture with albumin (1.0 mg/ml). This effect was not significantly altered in the presence of IGF-I (10(-9) or 10(-8) M). Alkaline phosphatase activity was significantly decreased by culture with albumin (0.5 or 1.0 mg/ ml), while it was significantly increased in the presence of IGF-I (10(-9) or 10(-8) M). The effect of IGF-I in increasing the enzyme activity was not significantly altered in the presence of albumin (0.5 or 1.0 mg/ ml). The effect of albumin (0.5 mg/ ml) plus IGF-I (10(-9) M) in increasing the cell number was completely prevented in the presence of PD98059, suggesting that the effect of albumin or IGF-I is partly mediated through mitogen-activated protein (MAP) kinase cascade. The expression of Runx2 (type 1) mRNA using transcription-polymerase chain reaction (RT-PCR) analysis in osteoblastic cells was significantly decreased by culture for 24 or 48 h with albumin (0.5 or 1.0 mg/ml) or IGF-I (10(-9) M). alpha1 (I) collagen mRNA expression in osteoblastic cells was significantly increased by culture for 24 h with albumin (0.5 or 1.0 mg/ml) or IGF-I (10(-9) M). Albumin (0.5, 1.0, or 2.0 mg/ml) did not have a significant effect on osteoclast-like cell formation induced by culture with parathyroid hormone (PTH; 10(-7) M) in mouse marrow culture. This study demonstrates that albumin has a role in the regulation of Runx2 or alpha1 (I) collagen mRNA expression, which may be mediated through intracellular signaling pathway, in osteoblastic cells.
Int J Mol Med 2005 Oct
PMID:Albumin regulates Runx2 and alpha1 (I) collagen mRNA expression in osteoblastic cells: comparison with insulin-like growth factor-I. 1614 6

Human serum albumin (HSA) is an abundant plasma protein that binds a remarkably wide range of drugs, thereby restricting their free, active concentrations. The problem of overcoming the binding affinity of lead compounds for HSA represents a major challenge in drug development. Crystallographic analysis of 17 different complexes of HSA with a wide variety of drugs and small-molecule toxins reveals the precise architecture of the two primary drug-binding sites on the protein, identifying residues that are key determinants of binding specificity and illuminating the capacity of both pockets for flexible accommodation. Numerous secondary binding sites for drugs distributed across the protein have also been identified. The binding of fatty acids, the primary physiological ligand for the protein, is shown to alter the polarity and increase the volume of drug site 1. These results clarify the interpretation of accumulated drug binding data and provide a valuable template for design efforts to modulate the interaction with HSA.
J Mol Biol 2005 Oct 14
PMID:Structural basis of the drug-binding specificity of human serum albumin. 1616 13

Albumin, the most abundant protein components of blood plasma, is synthesized and secreted by liver cells in vertebrates. Recently, it was demonstrated that frog Bombina maxima albumin is also expressed in skin. Both B. maxima albumins from skin and serum (BmA-skin and BmA-serum) have similar biochemical characteristics except that the former contains haem b. Present studies showed that BmA-skin exhibited cytotoxic activity on H9 and C8166 cells. Pretreated with hemin to induce erythroid differentiation, K562 cells lost their resistance to cytotoxicity of BmA-skin. After treating cells with BmA-skin for 48 h, 50 percentage cytotoxic concentrations (CC(50)) of BmA-skin on H9, C8166 and hemin-treated K562 cells were 1.31+/-0.09, 1.59+/-0.08 and 2.28+/-0.06 microM, respectively. The cell death induced by BmA-skin was mediated by apoptosis of the tested cell lines, as demonstrated by nuclear morphological changes, DNA fragmentation and DNA hypodiploidy of apoptosis cells. At BmA-skin concentration of 2 microM, 27.3%, 19.7% and 17.8% of H9, C8166 and hemin-treated K562 cells were found to be apoptotic. In contrast, BmA-serum possessed no cytotoxic and apoptosis-inducing activity on all the cell lines tested, even with concentration used up to 15 microM. These results indicated that bound haem b in BmA-skin contributed significantly to its cytotoxic and apoptosis-inducing activity on the cell lines assayed.
Comp Biochem Physiol B Biochem Mol Biol 2006 Feb
PMID:Apoptotic activity of frog Bombina maxima skin albumin. 1634 64

Human serum albumin (HSA) is an abundant plasma protein that transports a wide variety of drugs and endogenous compounds. The complex binding capacity of HSA has made it a challenging system to study in detail but in order to develop our understanding of the interactions between ligands for HSA, the locations and relative affinities of different ligand binding sites must be determined. Albumin possesses multiple binding sites for its primary physiological ligand, non-esterified fatty acids (FA). Previously, titration of BSA with (13)C-labeled FA revealed multiple chemical shifts and allowed identification of a subset of three chemical shifts that were associated with high affinity FA binding. Recent crystallographic studies of HSA have mapped at least seven FA binding sites for long-chain FA and delineated the overlap with binding sites for drugs and other endogenous compounds. We aim to correlate NMR and structural data for FA to provide a more complete description of the binding capacity of HSA. Our recent mutagenesis studies allowed us to identify two high affinity binding sites in domain III of HSA. Here, we use NMR to study the binding of (13)C-carboxyl labeled palmitate to HSA in the presence and absence of competitor ligands to complete the correlation of NMR chemical shifts with specific structural binding sites. We carefully selected ligands with specific binding sites identified by crystallography and used them, either singly or in combination, to compete with [(13)C]palmitate for binding to HSA. We show that FA sites 2, 4 and 5 bind FA with high affinity, while sites 1, 3, 6 and 7 exhibit low affinity for FA, thus providing the first complete determination of relative affinities of all seven long-chain FA sites on HSA. Our results also yield direct insights into the interactions between FA and other ligands.
J Mol Biol 2006 Aug 11
PMID:Location of high and low affinity fatty acid binding sites on human serum albumin revealed by NMR drug-competition analysis. 1684 40

Human serum albumin is the most abundant protein in the circulatory system, and one of its principal functions is to transport fatty acids. Binding of octanoate, decanoate, laurate and myristate was studied by a rate-of-dialysis technique. The primary association constants increased, but not linearly, with chain length. The number of high-affinity sites also increased with chain length; octanoate and decanoate bind to one such site, whereas laurate and myristate most probably bind to two sites. Albumin is composed of three homologous helical domains (I-III), which can be subdivided into two subdomains (A and B). For getting information about the positions of the high-affinity sites we produced 13 recombinant isoforms mutated in four different subdomains. Results obtained with these albumins are in accordance with the following model: octanoate and decanoate bind to a single site in subdomain IIIA, laurate binds to sites in subdomains IIIA and IIIB, whereas myristate binds in subdomains IB and IIIB. The results also showed that primary fatty acid binding is sensitive to amino acid substitutions in other parts of the protein. This is in contrast to the effect of amino acid substitutions of genetic albumin variants (alloalbumins). Usually these substitutions, which are situated at the surface of the protein, have no effect on fatty acid binding. Binding of fatty acid anions to different high-affinity sites and the sensitivity of these sites to amino acid substitutions elsewhere in the protein (and perhaps also to other types of modifications) are important factors that could effect simultaneous binding of other ligands, e.g. in patients treated with albumin-binding drugs.
J Mol Biol 2006 Oct 27
PMID:Chain length-dependent binding of fatty acid anions to human serum albumin studied by site-directed mutagenesis. 1697 83

Increased reactive oxidant intermediates (ROIs) from primed leukocytes have been implicated in the pathogenesis of acid aspiration lung injury. To evaluate the specific role of the phagocyte NADPH oxidase-derived ROIs in acid lung injury, the p47phox-/- knockout mouse model of chronic granulomatous disease was used. p47phox-/- mice developed a significantly greater alveolar neutrophilic leukocytosis compared with wild-type mice at all time points after acid injury, with the difference between genotypes being most marked at 48 h. In contrast, the p47phox-/- mice had a decreased number of macrophages in bronchoalveolar lavage (BAL) compared with wild-type at 48 h after acid or saline aspiration. Albumin concentration in BAL reflecting capillary leak was also greater in p47phox-/- compared with wild-type mice. BAL concentrations of proinflammatory cytokines and chemokines were greater in p47phox-/- compared with wild-type mice. These findings suggest that NADPH oxidase, directly or indirectly, plays a role in attenuating the acute neutrophilic response after acid lung injury. We speculate that this downmodulating effect may be mediated by promoting the transition from production of cytokines and chemokines involved in neutrophilic infiltration to a less injurious, chronic inflammatory response.
Am J Physiol Lung Cell Mol Physiol 2007 Mar
PMID:Acid aspiration-induced lung inflammation and injury are exacerbated in NADPH oxidase-deficient mice. 1711 80

The goal of this work is to identify novel serum proteins that are labeled with organophosphates (OPs) and to create a protocol for identification using mass spectroscopy. The use of OP-labeled proteins for identification of exposure is useful because such proteins will remain in circulation for weeks (Van Der Schans et al., 2004). Currently, both butyrylcholinesterase (BChE) and albumin have been shown to bind OPs in blood. Peeples et al. (2005) showed that albumin is labeled by OPs, specifically 6-Nbiotinylaminohexyl isopropyl phosphorofluoridate hemihydrate, in living mice. Albumin is the major protein in human serum, and its reaction with OPs tends to overwhelm the identification of other proteins. In vitro studies of human serum require removal of the serum albumin without depleting the less abundant proteins. Following this step, identifying the remaining proteins is simply a matter of labeling the proteins with an OP, separating the labeled from nonlabeled proteins, and using Q-trap mass spectrometry for identification.
J Mol Neurosci 2006
PMID:Markers of organophosphate exposure in human serum. 1719 43

Lobe-finned fish, particularly lungfish, are thought of as the closest extant relatives to tetrapods. Albumin, the major vertebrate plasma protein, has been well studied in tetrapods, but there exists no comparative study of the presence and characteristics of albumin in lobe-finned fish versus other vertebrates. There is a controversy over the presence of albumin in fish, although it is present in salmonids and lamprey. The presence of albumin in lungfish has also recently been documented. We identified albumin in plasma of the Australian lungfish, Neoceratodus forsteri, using a combination of agarose gel electrophoresis, [(14)C]palmitic acid binding and SDS-PAGE. Lungfish albumin was purified using DEAE-ion exchange chromatography, and has a mass of 67 kDa, is present at approximately 8 g/L in plasma and like other fish albumins, does not bind nickel. However, like tetrapod albumins, it is not glycosylated. N-terminal and internal peptide sequencing generated 101 amino acids of sequence, which showed a high degree of identity with tetrapod albumins. Despite the similarity in sequence but congruent with the evolutionary distances separating them, lungfish albumin did not cross-react with anti-chicken or anti-tuatara A albumin antisera. Lungfish albumin has characteristics more akin with tetrapod albumin and less like those of other fish.
Comp Biochem Physiol B Biochem Mol Biol 2007 Jul
PMID:Lungfish albumin is more similar to tetrapod than to teleost albumins: purification and characterisation of albumin from the Australian lungfish, Neoceratodus forsteri. 1740 5


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