Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0393754 (HSA)
 2,996 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Optimal activation of T cells often requires signals delivered by the ligation of T cell receptor (TcR) and those resulting from costimulatory interaction between certain T cell surface accessory molecules and their respective counter receptors on antigen presenting cells. The molecular events underlying the co-stimulatory activity are still not understood fully. Here we describe a 38-42-kDa (B3) protein, present on the surface of lipopolysaccharide-activated B cells, which can provide co-stimulation to resting T cells leading to a predominant release of interleukin (IL)-4 and IL-5 and negligible amounts of IL-2 and interferon-gamma. Binding assay and electron microscopic autoradiography data suggest that this molecule binds T cells, and the same can be competed by unlabeled B3. Characterization experiments point out that B3 shows up as a single prominent peak on reverse phase-high performance liquid chromatography, runs as a single spot in reducing two-dimensional gel electrophoresis, and is a phosphoglycoprotein. The Western analysis indicate that it does not cross-react with antibodies directed against murine ICAM-1, LFA-1 alpha, VCAM-1, HSA, and B7 suggesting the novelty of the protein. The internal amino acid sequence of this molecule suggests that it does not belong to a known category of murine B cell surface molecules.
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PMID:Characterization of novel costimulatory molecules. A protein of 38-42 kDa from B cell surface is concerned with T cell activation and differentiation. 755 3

The initiation of T cell responses against antigens requires two distinct signals. The first, the essential signal is the engagement of T cell receptor to antigen peptide in the context of MHC molecules on antigen presenting cells (APC). The presence of the second signal (costimulatory signal) determines whether responding T cells to be fully responsive or to be anergic (antigen specific nonresponsiveness). There are numbers of such costimulatory receptor/ligand pairs including B7/CD28: CTLA4, VCAM-1/VLA4, ICAM-1/LFA-1, HSA/unknown, and LFA-3/CD2. Among those ligand receptor pairs, B7/CD28 pathway is chosen and the molecular mechanism how T cell responses are regulated by B7/CD28 is discussed.
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PMID:[The molecular mechanism of costimulatory signal for T cell activation]. 853 79

Optimal activation of T cells to clonally expand requires at least two distinct biological signals; one is generated by the interaction of the T cell receptor (TcR) with peptides bound to MHC molecules. The other signal(s) is (are) generated by a functionally defined event called the co-stimulatory pathway. We have characterized the co-stimulatory property of a murine B lymphocyte membrane protein (155-160 kD) on resting CD4+ T cells. The study involved the isolation of a 155-160 kD protein (B1) from the membranes of LPS-stimulated B cells. When reconstituted into lipid vesicles, B1 exerted a dose-dependent proliferative response to CD4+ T cells, resulting in the predominant secretion of IL-4 and IL-5 after cross-linking receptors with anti-CD3 mAb. This protein is a phosphoglycoprotein which gives a single spot on two-dimensional gel electrophoresis under reducing conditions and as a distinct peak on reverse phase-HPLC. The B1 binds to the T cell surface as is demonstrated by electron microscopic autoradiography and scanning electron microscopy, as well as competitive binding assays. It does not cross-react with antibodies directed against ICAM-1, LFA-1 alpha, B7, HSA and VCAM-1, suggesting the novelty of the protein. Activation of CD4+ T cells with B1 in the presence of anti-CD3 resulted in the translocation of protein kinase C (PKC). The B1 is barely detectable on the surface of resting B cells and digestion of this protein with V8 protease and peptide N-glycosidase F resulted in distinct protein bands on an autoradiogram.
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PMID:Characterization of a novel co-stimulatory molecule: a 155-160kD B cell surface protein provides accessory help to CD4+ T cells to proliferate and differentiate. 860 18

The accumulation of advanced oxidation protein products (AOPPs) has been linked to vascular lesions in diabetes, chronic renal insufficiency, and atherosclerosis. However, the signaling pathway involved in AOPPs-induced endothelial cells (ECs) perturbation is unknown and was investigated. AOPPs modified human serum albumin (AOPPs-HSA) bound to the receptor for advanced glycation end products (RAGE) in a dose-dependent and saturable manner. AOPPs-HSA competitively inhibited the binding of soluble RAGE (sRAGE) with its preferential ligands advanced glycation end products (AGEs). Incubation of AOPPs, either prepared in vitro or isolated from uremic serum, with human umbilical vein ECs induced superoxide generation, activation of NAD(P)H oxidase, ERK 1/2 and p38, and nuclear translocation of NF-kappaB. Activation of signaling pathway by AOPPs-ECs interaction resulted in overexpression of VCAM-1 and ICAM-1 at both gene and protein levels. This AOPPs-triggered biochemical cascade in ECs was prevented by blocking RAGE with either anti-RAGE IgG or excess sRAGE, but was not affected by the neutralizing anti-AGEs IgG. These data suggested that AOPPs might be new ligands of endothelial RAGE. AOPPs-HSA activates vascular ECs via RAGE-mediated signals.
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PMID:Advanced oxidation protein products activate vascular endothelial cells via a RAGE-mediated signaling pathway. 1857 17

Most of the studies on advanced glycation end products (AGE) have been carried out with uncharacterized mixtures of AGE, so the observed effects cannot be linked to defined structures. Therefore, we analysed the structural differences between glycated human serum albumin (gHSA), a low glycated protein, and AGE-human serum albumin (AGE-HSA), a high glycated protein, and we compared their effects on endothelial functionality. Specifically, we characterized glycation and composition on both early and advanced stage glycation products of gHSA and AGE-HSA by using the MALDI-TOF-mass spectrometry assay. Furthermore, we studied the effects of both types of glycation products on reactive oxygen species (ROS) production and in the expression of vascular and intercellular cell adhesion molecules (VCAM-1 and ICAM-1) on human umbilical endothelial cells (HUVEC). We also measured the adhesion of peripheral blood mononuclear cells (PBMC) to HUVEC. Low concentrations of gHSA enhanced long-lasting ROS production in HUVEC, whereas lower concentrations of AGE-HSA caused the anticipation of the induced extracellular ROS production. Both gHSA and AGE-HSA up-regulated the expression of VCAM-1 and ICAM-1 at mRNA levels. Nevertheless, only AGE-HSA increased protein levels and enhanced the adhesion of PBMC to HUVEC monolayers. Functional differences were observed between gHSA and AGE-HSA, causing the latter an anticipation of the pro-oxidant effects in comparison to gHSA. Moreover, although both molecules induced genetic up-regulation of adhesion molecules in HUVEC, only the high glycated protein functionally increased mononuclear cell adhesion to endothelial monolayers. These observations could have important clinical consequences in the development of diabetic vascular complications.
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PMID:Key structural and functional differences between early and advanced glycation products. 2658 Dec 38