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At least 19 recordsLinked to original sources
PubMed1992

Genetic polymorphisms of alpha-2-HS-glycoprotein, group-specific component and orosomucoid in the Han population, Chengdu, China.

The Han population in Chengdu, China, was investigated for genetic polymorphisms of alpha-2-HS-glycoprotein (A2HS), group-specific component (GC) and orosomucoid (ORM) using isoelectric focusing followed by immunofixation. The allele frequencies were: A2HS*1 = 0.6958,A2HS*2 = 0.3042, GC*1F = 0.4021, GC*1S = 0.3182, GC*2 = 0.2745, GC*1A = 0.0052, ORM1*F1 = 0.7028, ORM1*S = 0.2762, ORM1*F2 = 0.0210, ORM2*A = 0.9965, ORM2*Var = 0.0035.

Alleles↗
PubMed1992

Polymorphisms of alpha-1-acid (orosomucoid), alpha-2-HS-glycoproteins and alpha-1-B among the Parsis of India.

Genetic polymorphisms of plasma alpha 1-acid glycoprotein (oro-somucoid, ORM), alpha 2-HS-glycoprotein (A2HS) and alpha 1-B-glycoprotein (alpha 1B) were studied in a group of Parsis in Bombay, India. The frequencies of ORM1*1, ORM1*2 and ORM1*3 were found to be 0.636, 0.356 and 0.008, respectively. A2HS*1, A2HS*2 and A2HS*3 frequencies were 0.855, 0.135 and 0.010, while the frequencies of A1B*1 and A1B*2 were 0.881 and 0.119, respectively. The phenotype distribution at all three loci was at Hardy-Weinberg equilibrium. The ORM2 locus was monomorphic in the Parsis.

Alleles↗
PubMed1978

Quantitative determination of single serum proteins during acute hepatitis in childhood.

Fifteen serum proteins were estimated by linear immunodiffusion in blood samples from children with acute hepatitis. Blood was drawn at the beginning of the disease and three weeks later. The results were compared with results obtained from a group of age-matched normal children. At the beginning of the disease prealbumin and beta-2-glycoprotein I were depressed, whereas alpha-1-acid-glycoprotein, alpha-1-antitrypsin, cerloplasmin and alpha-2-HS-glycoprotein were found to be elevated. Alpha-2-macroglobulin, transferrin and beta-lipoprotein showed a significant elevation after three weeks. Beta-1-A/C, IgM and IgG remain elevated during time of observation. Albumin, haptoglobin and IgA were similar in patients and controls and did not change during the period of observation.

Acute Disease↗
PubMed1979

Isolation and renal localisation of urokinase.

Physico-chemical characteristics of urokinase in urine were studied by immunological and chemical methods. By agar zone electrophoresis, commercial urokinase preparations could be separated into an anodic and cathodic fraction. The latter reacted with urokinase antibodies with two precipitation bands. Band I displayed the major part of urokinase activity and migrated as a beta-globulin with a molecular weight of 32,000 daltons. Band II showed immunological identity with human serum, human albumin, alpha-2-macroglobulin and alpha-2-HS-glycoprotein. The specific activity of the cathodic fractions was up to 80,000 ploug units/mg protein. The ratio esterase/fibrinolytic activity did not change during the purification procedure. Further purification of the fractions with higher specific activity by affinity chromatography was unable to eliminate material cross reacting with human antisera (Band II). These findings permit the conclusion, that urokinase activity in urine is not confined to a homogeneous protein fraction. Activity is found both in a low molecular weight fraction and in a high molecular weight complex which contains serum proteins. These cannot be removed by exhaustive purification procedures and may play an important role in stabilizing and/or protecting urinary urokinase against proteolytic degradation. With Todd's technique diffuse fibrinolytic activity could be demonstrated in the kidney in the iuxtamedullary border region, (venae arcuatae, venae interlobulares, vasa recta) and in the epithelium of the calyces. Urokinase activity was specifically blocked by highly purified urokinase antibodies and could thus be distinguished from nonspecific proteolytic activity. The topographic relationship to medulla and uroepithelium may point to a role of urokinase in maintaining patency in slow flow systems.

Endopeptidases↗
PubMed1992

Fetuin--an old friend revisited.

Bovine fetuin, the first fetal protein to be described, has recently been shown to be a species homologue of a well known human plasma protein--alpha 2HS glycoprotein (alpha 2HS). The fetuins are now known to be members of the cystatin superfamily. The structural properties of the six fetuins that have been fully sequenced are compared. Despite the structural homology of these proteins, their described properties in the literature make them appear to be quite different. The diverse in vitro properties claimed for fetuin/alpha 2HS are reviewed. In vivo, fetuins are involved in the acute phase response. In development, in all species studied so far, fetuins are present in a specific cell population that forms the developing neocortex. The possible functional significance of this distribution is discussed.

Acute-Phase Reaction↗
PubMed1992

Genetic variation in two bone-related proteins: is there an association with bone mineral density or skeletal size in postmenopausal women?

In an effort to determine if structural variation in proteins important in bone metabolism might influence bone mineral density (BMD) and thus be a determinant of susceptibility to osteoporosis in older women, the authors typed a group of 258 non-Black women (age 65-90) participating in the Study of Osteoporotic Fractures (SOF) for two polymorphic bone-related proteins, group specific component (Gc), also known as vitamin D-binding protein, and alpha 2HS glycoprotein (AHSG). These two proteins exhibit common structural variation in populations that can be detected by isoelectric focusing/immunoblotting of serum. An important function of Gc is the binding, solubilization, and transport of vitamin D sterols in the bloodstream while AHSG is a glycoprotein constituent of calcified cortical bone matrix. There are six common phenotypes of Gc and four of AHSG. Using Gc or AHSG phenotypes as categorical variables, statistical analyses were done to determine if bone mineral density of the proximal or distal radius or calcaneus differed by phenotype. Neither Gc nor AHSG phenotype demonstrated a statistically significant relationship with BMD at any site. Adjustments for age and degree of obesity did not substantively affect these results. Subsequent analyses to determine if phenotype of either of these proteins was associated with variables related to skeletal size showed an association of AHSG with height (P less than .02). This may indicate that AHSG phenotype is related to postmenopausal loss of height, or it may be a chance statistical finding.

Aged↗
PubMed1992

Formal and population genetic studies of AHSG: further data from Galicia.

A sensitive immunodetection method for Alpha-2-HS glycoprotein (AHSG) after ultrathin layer polyacrylamide gel isoelectric focusing has been applied to a family study of 126 matings including 292 offspring. Formal genetic studies are in agreement with an autosomal mode of inheritance for this system. A population study of 506 unrelated individuals from Galicia (NW Spain) gave the following frequencies: AHSG*1 = 0.7559 and AHSG*2 = 0.2441, which correspond to a exclusion chance for non-fathers of 0.1505.

Adult↗
PubMed1992

Genetic polymorphism of human alpha 2 HS-glycoprotein (AHSG) in the resident population of the Basque Country (northern Spain).

The genetic polymorphism of human alpha 2 HS-glycoprotein (AHSG) was studied in a sample of 466 healthy unrelated individuals resident in the Basque Country (Northern Spain) by isoelectric focusing on micro-ultrathin polyacrylamide gels followed by immunoblotting. The allele frequencies obtained were AHSG*1 = 0.7253, AHSG*2 = 0.2683 and AHSG*3 = 0.0064. These allele frequencies were compared with those reported in other European populations.

Blood Proteins↗
PubMed1992

Pause transfer: a topogenic sequence in apolipoprotein B mediates stopping and restarting of translocation.

Previously, we described the stepwise translocation of a large amino-terminal fragment of apolipoprotein B (apo B15) in which the nascent secretory chain translocates through a series of distinct, nonintegrated transmembrane intermediates with large domains exposed to the cytoplasm. Thus, apo B15 appears to stop and restart translocation at several points. We have identified a sequence of amino acids in apo B15 that confers this behavior on a heterologous chimeric protein. In addition, we dissect pausing into two distinct steps, stopping and restarting, thereby trapping otherwise transient intermediates. Finally, we demonstrate the function of a second "pause transfer" sequence over 200 amino acids downstream in apo B15 that restarts translocation posttranslationally, suggesting that multiple pause transfer sequences are involved in the biogenesis of apolipoprotein B.

Amino Acid Sequence↗
PubMed1992

Human alpha 2-HS-glycoprotein/bovine fetuin homologue in mice: identification and developmental regulation of the gene.

Human alpha 2-HS-glycoprotein (AHSG) is a plasma protein synthesized in liver and selectively concentrated in bone matrix. It has been reported to be involved in bone formation and resorption as well as immune responses. Recently, AHSG was found to be the species equivalent protein of fetuin, the major fetal serum protein in cattle and sheep. The function and regulation of AHSG/fetuin in different species are not understood. We have isolated a liver cDNA clone that encodes the human AHSG/bovine fetuin homologue in the mouse. The AHSG/fetuin gene may have a role in differentiation since it is expressed in mouse limb buds and brain only at certain stages during development. Mouse liver AHSG/fetuin mRNA was present at low level at 12 days gestation but its level increased during the late part of gestation and peaked between 1 to 3 months after birth. The regulation of mouse AHSG/fetuin synthesis during development was found to be significantly different from that of sheep and bovine fetuin. Compared to fetuin, which is reduced in adult to 1 to 2% of the fetal level, mouse AHSG synthesis subsides only 50% 4 months after birth.

Amino Acid Sequence↗
PubMed1991

Expression of the pp63 gene encoding the insulin receptor tyrosine kinase inhibitor in proliferating liver and in liver tumors.

After partial hepatectomy in rats, a approximately 4-fold decrease in pp63 mRNA level was detected at 24 h, but not at earlier time points. In mice, during liver cell proliferation induced by 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene and phenobarbital, pp63 transcript levels had a decrease of 40-50%. However, pp63 mRNA was 5-6 fold higher in murine hepatocellular tumors than in normal adult mouse liver.

Animals↗
PubMed1992

Comparison of N-glycosides of fetuins from different species and human alpha 2-HS-glycoprotein.

Complex type N-glycosides of commercial bovine fetuin preparations from pooled fetal calf serum have been shown to contain comparable amounts of Gal4,4,4TRI (see structure A below) and Gal4,4,3TRI (structure B) as major asialo-structures. To investigate whether there is a clear genetic specificity for synthesis of these oligosaccharides, N-glycosides from two preparations of bovine fetuin, each from a single calf, were examined. Both of these structures were present in each calf, and there was only a subtle quantitative difference in the ratio of these two structures between the calves. Thus, a specific galactosyltransferase, presumably required for the biosynthesis of the Gal4,4,3TRI structure, may exist in both of these individual calves. Comparison of fetuin N-glycosides was also extended to sheep, pig, and human alpha 2-HS-glycoprotein, the human counterpart of bovine fetuin, using high-pH anion-exchange chromatography of the reducing oligosaccharides as well as HPLC of their pyridinylamino derivatives. The N-glycosides of ovine fetuin also have both Gal4,4,4TRI and Gal4,4,3TRI structures in a ratio similar to that of bovine fetuin. However, the major N-glycoside of porcine fetuin is of a fucosyl biantennary complex type structure (structure C below) and human alpha 2-HS-glycoprotein has an N-glycoside which is almost exclusively a nonfucosylated biantennary structure (structure D). This species-specific presence of N-glycosides of fetuins and comparison with N-glycosides of other glycoproteins suggest that the polypeptide sequence of a glycoprotein may affect its N-glycan structure by regulating the activity of specific glycosyltransferases. [formula: see text]

Amidohydrolases↗
PubMed1992

Structure of the N- and O-glycans of the A-chain of human plasma alpha 2HS-glycoprotein as deduced from the chemical compositions of the derivatives prepared by stepwise degradation with exoglycosidases.

The structure of the glycans of the A-chain of human plasma alpha 2HS-glycoprotein was established from the chemical compositions of its derivatives prepared by sequential enzymatic degradation of the carbohydrate moiety, from the determination of the kind and amount of the monosaccharides liberated after each step of the enzymatic digestion, and from the distinct specificity of the highly purified exoglycosidases. The exoglycosidases were three sialidases (Vibrio cholerae, fowl plague virus, and Arthrobacter ureafaciens), two beta-galactosidases (Streptococcus pneumoniae and bovine testis), one alpha-N-acetylgalactosaminidase, one beta-N-acetylglucosaminidase, and one alpha-mannosidase. Utilizing sialidases with different cleavage specificities, the number of alpha 2-3- and alpha 2-6-linked sialic acid residues could be separately determined. As to the beta-galactosidases, the enzyme isolated from S. pneumoniae cleaves only beta 1-4-linked galactose residues, whereas the bovine testes enzyme acts on both the beta 1-4- and beta 1-3-linked galactose residues. Jack bean beta-N-acetylglucosaminidase cleaves beta 1-2, beta 1-4, and beta 1-6 GlcNAc with higher activity for the beta 1-2. Jack bean alpha-mannosidase cleaves alpha 1-2, alpha 1-6, and alpha 1-3 Man with greater activity for alpha 1-2 and alpha 1-6. Bovine liver alpha-N-acetylgalactosaminidase cleaves O-linked GalNAc. On the basis of these results, the A-chain of alpha 2 HS-glycoprotein was found to possess two biantennary N-glycans and two O-linked trisaccharides.

Blood Proteins↗
PubMed1991

Rat tyrosine kinase inhibitor shows sequence similarity to human alpha 2-HS glycoprotein and bovine fetuin.

Human alpha 2-HS glycoprotein and bovine fetuin, abundant proteins of fetal plasma, are structural members of the fetuin family within the cystatin superfamily. They are characterized by the presence of two N-terminally located cystatin-like units and a unique C-terminal sequence segment not present in the other members of the cystatin superfamily. Search for related sequences revealed that the natural inhibitor of the insulin receptor tyrosine kinase [Auberger, Falquerho, Contreres, Pages, Le Cam, Rossi & Le Cam (1989) Cell (Cambridge, Mass.) 58, 631-640] shows sequence similarity to the mammalian fetuins. The sequence identity between rat tyrosine kinase inhibitor, human alpha 2-HS glycoprotein and bovine fetuin is 56 and 60% respectively (percentage of residues in identical positions). The sequence similarity extends over the entire protein structures, except the extreme C-terminal portions. In particular, the number and relative positions of the cysteine residues are invariant among the proteins, suggesting that the characteristic array of linearly arranged and tandemly repeated disulphide loops of the cystatin superfamily is also present in rat tyrosine kinase inhibitor. We conclude that rat tyrosine kinase inhibitor may be classified as a novel member of the mammalian fetuin family.

Amino Acid Sequence↗
PubMed1992

The human hepatoma Hep3B cell line as an experimental model in the study of the long-term regulation of acute-phase proteins by cytokines.

The regulation of the synthesis by the cytokines interleukin-1 (IL-1) and IL-6 of the positive acute-phase protein alpha 1-acid glycoprotein (AGP) and of the negative acute-phase protein alpha 2-HS glycoprotein (AHSG) has been studied in a long-term culture system of the human hepatoma cell line Hep3B. The culture system contained 30 nM-sodium selenite as the only supplement. This allowed maintenance of the synthesis of the proteins under study at a near steady state for over 3 months. An increase in AGP mRNA and a decrease in AHSG mRNA were observed when cells were treated for two successive 48 h-periods with monocyte-conditioned medium. A return to basal levels was obtained after cessation of the cytokine addition. Two further additions of cytokines led to alterations in mRNA levels similar to those observed following the first cytokine treatment. The amounts of AGP and AHSG secreted were altered in accordance with the mRNA modifications. These results suggest that new cytokine receptors were being constantly synthesized during cell culture. When cytokines were present in the culture medium for 10 days, maximum alterations in AGP and AHSG synthesis were obtained following 2 and 4 days of treatment respectively, but further alterations in protein levels could not be observed afterwards. Expression of IL-6 receptor mRNA was not up-regulated by cytokines, but only by 1 microM-dexamethasone. Our results show that, in this long-term culture system, cytokines induce a response in hepatoma cells similar to that observed in vivo during human inflammatory states. This model could be used to evaluate the effects of agonists or antagonists of cytokines responsible for the hepatic acute-phase protein response.

Acute-Phase Proteins↗
PubMed1992

Functional characterization of the promoter of pp63, a gene encoding a natural inhibitor of the insulin receptor tyrosine kinase.

PP63 is a liver specific phosphorylated glycoprotein encoded by a single copy gene, which has the property of inhibiting both autophosphorylation and tyrosine kinase activity of the insulin receptor. In this study, we have analyzed the structure activity relationship of the pp63 gene promoter. Five protein binding sites were found in the proximal 5' flanking region of the gene (-223 to +4). Using oligonucleotides as competitors and purified recombinant C/EBP in footprinting and gel retardation assays, we identified two typical C/EBP sites (X1 and X3) plus a heterogenous, C/EBP-NF1 like site (X5), separated by two classical NF1 binding sites (X2 and X4). C/EBP or the related proteins were predominantly involved in supporting cell-free transcription. Occupancy of the first high affinity C/EBP site conferred almost maximal promoter efficiency, in vitro. However, this pp63 promoter activity remained very low as compared to that in intact hepatocytes. In these cells, occupancy of the first C/EBP (X1) and NF1 (X2) sites was already required for achieving a weak transcriptional activity. The use of the second C/EBP site (X3) strongly enhanced transcription, up to 60-70% of the maximum, whereas occupancy of the two more distal sites (X4 and X5) was necessary to fully activate the promoter. Thus, the strength of the promoter as well as the liver specific expression of pp63 gene appear to result from the interplay of several DNA-protein complexes involving mainly C/EBP and/or related proteins as well as the ubiquitous NF1 factor(s), rather than from the interaction of a more liver specific trans-acting factor with the promoter.

Animals↗