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At least 19 recordsLinked to original sources
PubMed1988

Orosomucoid 1 and orosomucoid 2 types in the Taiwanese and Japanese: evidence for five new orosomucoid variants.

The genetic polymorphisms of orosomucoid, ORM1 and ORM2, were analyzed by isoelectric focusing on polyacrylamide gels and subsequent immunoprinting. Sera from 600 unrelated individuals in Taiwan and Japan were examined. Five new alleles, designated ORM1*7, ORM1*8, ORM1*4.2, ORM2*8 and ORM2*10, were observed together with common and rare alleles that have been found in the Japanese and the Filipinos. As compared with the Japanese, the Taiwanese have a higher frequency of ORM1*1, and a significantly lower frequency of ORM1*2.1.

Alleles↗
PubMed2005

Monitoring urinary orosomucoid in acute inflammation: observations on urinary excretion of orosomucoid, albumin, alpha1-microglobulin, and IgG.

BACKGROUND: Inflammation-associated proteinuria in acute, nonrenal disease is a common but poorly understood phenomenon. We performed an observational study of the urinary excretion of orosomucoid (alpha(1)-acid glycoprotein), albumin, alpha(1)-microglobulin (protein HC), and IgG to obtain quantitative and temporal data on these 4 proteins. METHODS: Urine samples were collected at daily intervals for up to 23 days from 6 patients with surgery-induced inflammation and at hourly intervals for a 24-h period from 7 sepsis patients. Urinary protein concentrations were assessed by immunoturbidimetry. RESULTS: During surgery-induced inflammation, the increase and decrease in orosomucoid excretion mirrored changes in plasma C-reactive protein. Values for all 4 urinary proteins were increased in sepsis patients. The observed maximum increases in urinary protein excretion relative to the upper reference values were 280-fold for orosomucoid, 98-fold for alpha(1)-microglobulin, 33-fold for albumin, and 26-fold for IgG. CONCLUSIONS: Orosomucoid, usually present in plasma and urine in much lower concentrations than albumin, is increased in urine to concentrations equal to or higher than albumin in proteinuria associated with acute inflammation. The pathophysiologic mechanisms responsible for this markedly increased excretion are unknown. Monitoring of urinary excretion of orosomucoid and other specific proteins, expressed as protein/creatinine ratios, may provide a window for clinically relevant real-time observation of changes in acute inflammatory processes. Orosomucoid in urine may be a more informative marker than albumin for inflammation.

Acute Disease↗
PubMed1994

[A new two-stage plan for isolating human alpha1-acidic glycoprotein (orosomucoid). Orosomucoid interacts with ethidium bromide].

Human alpha 1-acid glycoprotein (orosomucoid, AGP) was purified to homogeneity by a two-step procedure using phenol and chloroform deproteinization of serum with subsequent preparative electrophoresis on agarose gel. It was obtained 0.15-0.3 mg of protein from 1 ml of serum. Human alpha 1-AGP binds ethidium bromide but not DNA. Neither other human serum proteins nor mice and rat alpha 1-AGP bind ethidium bromide. This property of human orosomucoid depends on its amino acid sequence rather than on the carbohydrate part of the molecule.

Amino Acid Sequence↗
PubMed1990

Orosomucoid typing by isoelectric focusing: genetic variation of orosomucoid in Asian macaques (genus Macaca).

Genetic variation of orosomucoid (ORM) in the genus Macaca was investigated. Plasma samples were subjected to isoelectric focusing in a pH range of 4-6.5, followed by immunoprinting with anti-human ORM antibodies. A total of 25 alleles were identified in 231 Asian macaques belonging to 13 species from 23 populations and 22 members belonging to a family of M. fascicularis. Family data presented evidence for a codominant mode of inheritance with multi-alleles at a single autosomal locus. A population study revealed enormous intra- and interspecies variations. The heterozygosity values varied from 0.855 in M. fascicularis (Malaysia) to 0.000 in M. radiata (India), M. silenus (India) and M. arctoides (Malaysia).

Animals↗
PubMed1991

Orosomucoid typing of apes (family Pongidae) by isoelectric focusing: among primates do only humans have two functional orosomucoid loci?

It has been demonstrated that human orosomucoid (ORM) is controlled by more than one functional loci, while Macaca ORM is controlled by one locus. To examine the time when the ORM gene was duplicated in the evolution of primates, plasma samples from 118 apes (family Pongidae) belonging to 4 genera and 12 species were investigated for ORM polymorphism using isoelectric focusing followed by immunoprinting. The band patterns of ORM in the subfamily Ponginae showed quantitatively different products as in humans. A pedigree study of common chimpanzees supported the two-locus model for ORM. Gibbons (subfamily Hylobatinae) displayed highly variable band patterns, but the number of loci was not determined unequivocally. Thus, this study shows that duplication of the ORM gene in primates occurred either before or after the divergence of Hylobatinae and Ponginae, consistent with a previous prediction from the molecular evolutionary rate of ORM.

Alleles↗
PubMed1993

Orosomucoid system: 17 additional orosomucoid variants and proposal for a new nomenclature.

There are two forms of orosomucoid (ORM) in the sera of most individuals. They are encoded by two separate but closely linked loci, ORM1 and ORM2. A number of variants have been identified in various populations. Duplication and nonexpression are also observed in some populations. Thus, the ORM system is very complicated and its nomenclature is very confusing. In order to propose a new nomenclature, ORM variants detected by several laboratories have been compared and characterized by isoelectric focusing (IEF) followed by immunoprinting. A total of 57 different alleles including 17 new ones were identified. The 27 alleles were assigned to the ORM1 locus, and the others to the ORM2 locus. The designations ORM*F1, ORM1*F2, ORM1*S and ORM2*M were adopted for the four common alleles instead of ORM1*1, ORM1*3, ORM1*2 and ORM2*1 (ORM2*A), respectively. The variants were designated alpha numerically according to their relative mobilities after IEF in a pH gradient of 4.5-5.4 with Triton X-100 and glycerol. For the duplicated genes a prefix is added to a combined name of two alleles, e.g. ORM1*dB9S. Silent alleles were named ORM1*Q0 and ORM2*Q0 conventionally. In addition, the effects of diseases to ORM band patterns after IEF are also discussed.

Alleles↗
PubMed1985

Prazosin binding to human alpha 1-acid glycoprotein (orosomucoid), human serum albumin, and human serum. Further characterization of the 'single drug binding site' of orosomucoid.

The plasma protein binding of the alpha 1-adrenergic blocking agent prazosin was investigated by means of circular dichroism (CD) and equilibrium dialysis (ED) measurements. The interaction of prazosin with human alpha 1-acid glycoprotein (alpha 1-AGP) results in pronounced negative extrinsic Cotton effects at 255 nm and a smaller negative band at 285 nm which are associated with the binding of prazosin to only one site of the protein. Various basic drugs, and warfarin also, at 50 microM displace prazosin 10 microM from its binding site on alpha 1-AGP and reduce the CD-spectra at 255 nm by 26% (disopyramide), 52% (mepivacaine), about 70% (verapamil, biperiden), and 90-100% (trihexyphenidyl, warfarin). (+/-)-Propranolol reduces the CD-spectra by 76%, its (-)-isomer by 89%, and the (+)-isomer by 65%. ED experiments indicated that the binding of prazosin to alpha 1-AGP is saturable with an association constant of 48 000 M-1 and 0.85 binding sites per protein molecule. Displacement of prazosin from alpha 1-AGP by the same drug as used for the CD experiments at displacer/prazosin ratios of 5 resulted in comparable reductions of the fraction bound as obtained by the CD experiments. Prazosin was also highly bound to human serum albumin (600 microM) with about 80-85% bound at prazosin concentrations from 1-100 microM. Since prazosin binding to human serum is only slightly higher (80-90%) it is concluded that prazosin binding in serum is largely mediated by the albumin fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗
PubMed1974

Orosomucoid content of pleural and peritoneal effusions.

22 nonneoplastic, noninflammatory effusions (cirrhosis and congestive heart failure), 12 non-neoplastic inflammatory effusions (tuberculosis, lupus erythematosus, rheumatoid arthritis, and idiopathic pleuropericarditis), and 58 neoplastic effusions (cancer of lung, breast, ovary, and pancreas, and lymphoma) were analyzed by radial immunodiffusion for orosomucoid concentration. The average concentration +/-SE was 35+/-4, 65+/-17, and 130+/-13 mg/100 ml in the three types of effusion, respectively. By gel filtration and ion exchange chromatography, orosomucoid was isolated from 12 nonmalignant and 14 malignant fluids. The orosomucoid preparations reacted as single components in acrylamide gel electrophoresis at pH 9.0, and in immunodiffusion and immunoelectrophoresis against antisera to human serum and to human plasma orosomucoid. In radial immunodiffusion, the slope of the line relating concentration to the square of the diameter of the precipitate area was identical for orosomucoid isolated from normal human plasma and from nonneoplastic effusions, but was subnormal for orosomucoid isolated from neoplastic fluids. All orosomucoid preparations had normal amino acid composition. Orosomucoid from the nonmalignant effusions had normal carbohydrate content. 11 of 14 samples of orosomucoid isolated from neoplastic fluids had abnormalities in carbohydrate composition, consisting of subnormal content of sialic acid (11 of 14), hexose (10 of 14), and hexosamine (3 of 14), and abnormally high content of hexosamine (4 of 14). Discriminant analysis showed that concentration of orosomucoid distinguished between neoplastic and nonneoplastic noninflammatory effusions more effectively than concentration of total protein, albumin, alpha(1), alpha(2), beta, or gamma-globulin.

Albumins↗
PubMedDate not supplied

Microheterogeneity of orosomucoid in pathological conditions.

Studies of orosomucoid (alpha 1-acid glycoprotein) in human serum have revealed that orosomucoid is a mixture of molecules with differences in the glycan chains. This microheterogeneity has been studied using crossed affinoimmuno-electrophoresis with the lectin concanavalin A which binds to biantennary glycans. The relative proportions of the three orosomucoid subtypes are altered in various pathological conditions independently of the total serum orosomucoid concentration. There are reproducible differences in microheterogeneity patterns between some pathological conditions: Acute tissue injury or inflammation results in a high proportion of orosomucoid with biantennary glycans. Conditions with increased estrogen levels are associated with a high proportion of orosomucoid with tri- or tetraantennary glycans and a low total serum orosomucoid concentration. Chronic inflammation also seems to be associated with a high proportion of orosomucoid with tri- or tetraantennary glycans but with a high total serum concentration of orosomucoid. Other diseases, such as cancer, can not be associated with any specific microheterogeneity pattern. The microheterogeneity pattern in these conditions seems to be determined by disease activity and unspecific inflammation in surrounding tissues.

Concanavalin A↗
PubMed2002

Orosomucoid in urine predicts cardiovascular and over-all mortality in patients with Type II diabetes.

AIMS/HYPOTHESIS: Urinary orosomucoid excretion rate is increased in a substantial proportion of patients with Type II (non-insulin-dependent) diabetes mellitus and normal urinary albumin excretion rate. The aim of this study was to determine whether increased urinary orosomucoid excretion rate is predictive of increased mortality in patients with Type II diabetes. METHODS: In a cohort study including 430 patients with Type II diabetes, baseline urinary samples were analysed for orosomucoid and albumin. Mean follow-up was 2.4 years. RESULTS: We found that 188 (44 %) patients had normal and 242 (56 %) patients had increased urinary orosomucoid excretion rates. During the study period 41 patients died; out of these 23 patients died of cardiovascular diseases. Odds ratio for all-cause mortality was 2.50 (95 % CI 1.00-6.22) and odds ratio for cardiovascular mortality was 9.81 (1.31-73.6) having increased urinary orosomucoid excretion rate at baseline (odds ratios adjusted for age, sex, duration of diabetes, cardiovascular diseases, weight, medication, HbA1 c, plasma creatinine and urinary albumin excretion rate). Urinary albumin excretion rate was an independent predictor of all-cause mortality when urinary orosomucoid excretion rate was not included in the analysis. Subgroup analysis revealed that 39 % of the patients with normal urinary albumin excretion rate (n = 251) had increased urinary orosomucoid excretion rates and that these patients had a higher cardiovascular mortality (p = 0.007) than patients with normal urinary albumin excretion rate and normal urinary orosomucoid excretion rates. CONCLUSION/INTERPRETATION: We found that urinary orosomucoid excretion rate predicted all-cause and cardiovascular mortality in patients with Type II diabetes independently from other risk factors.

Albuminuria↗
PubMed1993

Addition of purified orosomucoid preserves the glomerular permeability for albumin in isolated perfused rat kidneys.

The serum protein, orosomucoid has been shown to be essential for the maintenance of normal capillary permeability in several different organs, including the kidney. Thus, the clearance of albumin was found to be almost fivefold higher in the absence of orosomucoid in a previous study on isolated rat kidneys, perfused with either of two commercially available human albumin solutions of similar composition, but differing in their content of orosomucoid (0.21 g l-1 vs. < 0.005 g l-1). The following experiments were performed in order to verify the hypothesis that this effect on glomerular permselectivity was due to orosomucoid per se and not to other ingredients in the two solutions. Both kidneys of 12 rats were isolated and perfused with identical albumin solutions without orosomucoid, but with the addition of purified orosomucoid (0.25 g l-1) to one of the kidneys. No significant differences in vascular resistance, urine flow or glomerular filtration rate (GFR), which was found to be 27 +/- 2 ml min-1 100 g-1, were observed between the two groups of kidneys. The fractional clearance of albumin (theta) was initially similar for both kidneys (0.0022 +/- 0.0002). In the absence of orosomucoid, theta gradually increased to 0.0076 +/- 0.0013 after 1 h of perfusion compared to 0.0040 +/- 0.0006 for the kidneys with orosomucoid added to the perfusate (P < 0.001, n = 12). We conclude that the plasma glycoprotein orosomucoid indeed plays an important role in regulating the dynamic properties of the glomerular capillary wall by reducing the permeability towards macromolecules such as albumin.

Albumins↗
PubMed1994

Capillary electrophoresis monitoring of the competitive adsorption of albumin onto the orosomucoid-coated polyisobutylcyanoacrylate nanoparticles.

The simultaneous and rapid quantitation of a glycoprotein, human orosomucoid, and a protein, human serum albumin (HSA), by micellar electrokinetic capillary electrophoresis was developed and optimized (pH and sodium dodecyl sulfate concentration) in order to study the competitive adsorption of HSA onto orosomucoid-coated nanoparticles of polyisobutylcyanoacrylate. This method provided satisfactory repeatability and the response was linear for concentrations of orosomucoid and HSA ranging from 0.025 to 0.500 mg/mL (r > 0.994 for both proteins). To study the competitive adsorption of HSA, the amounts of free orosomucoid and free HSA were determined in the supernatant obtained after centrifugation of the orosomucoid-coated nanoparticle suspension incubated with HSA. Furthermore, the quantities of both orosomucoid and HSA absorbed onto nanoparticles were also determined after desorption of these molecules from the nanoparticle surface, using sodium dodecyl sulfate. No analytical interference was observed with this surfactant. The results showed that HSA did not at all absorb onto the orosomucoid-coated nanoparticles and, thus, that this protein did not displace the layer of absorbed orosomucoid from the nanoparticle surface.

Adsorption↗
PubMed1983

Tissue locations for the turnover of radioactively labeled rat orosomucoid in vivo.

Tissues involved in the turnover of rat serum orosomucoid were identified by methods designed to cause lysosomal trapping of radiolabel at the sites of glycoprotein degradation. 125I-, [3H]Raffinose-, and [1-14C]glucosamine-labeled orosomucoid exhibited serum half-lives of 20, 20, and 27 h when injected intravenously into rats. As expected, the asialo derivative of [3H]raffinose-labeled rat orosomucoid was lost very rapidly from the circulation and recovered quantitatively in the liver within 30 min. At 50 h after injection of [3H]raffinose-asialo-orosomucoid the liver retained 38% of the radioactivity while the remainder was found in the gastrointestinal tract and urine. Chromatography of the urine on Bio-Gel P-4 revealed a single radioactive product that eluted similar to raffinose-lysine. The same material was found in the liver. This ability of the [3H]raffinose label to resist metabolic disposal was used to evaluate tissue catabolism of native rat orosomucoid. Comparison of the tissue radioactivity in experiments using 125I- and [3H]raffinose-labeled derivatives of the nondesialylated glycoprotein showed kidney, liver, and muscle to be most active in 3H accumulation. However, the [3H]raffinose metabolites excreted in the urine was markedly different from those produced from asialo-orosomucoid and in contrast there was minimal loss of label to the gastrointestinal tract from the native substrate. Leupeptin, an inhibitor of lysosomal thiol cathespins, was administered continuously to rats by a subcutaneous osmotic pump. At 24 h after injection of 125I-orosomucoid, leupeptin-treated rats showed a net 16% increase in tissue radioactivity above sham-operated animals and a corresponding decrease occurred in the radioactivity associated with the gastrointestinal tract and urine. Tissues that exhibited increases in radioactivity were kidney, muscle, liver, and hide. The different behavior of labeled native and asialo-orosomucoids suggests that the hepatic galactose receptor system plays, at most, a limited role in maintaining homeostasis of the native glycoprotein.

Animals↗
PubMed2006

Beneficial effects of orosomucoid on the glomerular barrier in puromycin aminonucleoside-induced nephrosis.

BACKGROUND: In a hitherto unconfirmed report, orosomucoid was reported to ameliorate the nephrotic syndrome induced by puromycin aminonucleoside (PAN) in rats. METHODS: We wanted to test this hypothesis and extend the analysis of the effects on the glomerular barrier. Glomerular filtration rate (GFR), and fractional clearance for albumin (theta(albumin)) and for neutral Ficolls were estimated in cooled isolated perfused kidneys. Modern transport equations were used to estimate glomerular size selectivity and charge selectivity. Also, podocyte morphology was studied. Four groups of rats (4 x n = 8) were administered PAN intraperitoneally and treated daily for 5 days with orosomucoid in two different doses (groups A and B), albumin (group C) or saline (group D). Two additional groups of rats (2 x n = 8) were used as controls and these rats received either saline (group E) or orosomucoid (group F) but no PAN. RESULTS: Treatment with orosomucoid restored podocyte morphology and renal function from the damaging effects of PAN in a dose-dependent manner. GFR was significantly reduced by PAN (groups C and D) when compared with controls (groups E and F). This effect was partly (group A) or completely (group B) reversed by orosomucoid. The theta(albumin) was 0.002+/-0.001 (mean+/-SEM) in controls (group E) and was unaffected by orosomucoid per se (group F). PAN increased theta(albumin) to 0.020+/-0.001 in group C and to 0.021+/-0.001 in group D, while it was significantly less in group A, 0.014+/-0.001, P<0.05. The heterogeneous charged fibre model analysis revealed that PAN reduced the relative volume of negatively charged fibres, phi, from 7.1+/-0.08% (group E) to 48% of this value in groups C and D (P<0.001); phi was 4.5+/-0.04% in group A, 5.3+/-0.44% in group B, and 6.1+/-0.11% in group F. CONCLUSION: High doses of orosomucoid completely normalized the glomerular barrier in six out of eight animals with puromycin-induced nephrotic syndrome. Thus, orosomucoid has a promising therapeutic potential for certain kidney disorders.

Analysis of Variance↗
PubMed1999

Human endothelial cells produce orosomucoid, an important component of the capillary barrier.

The serum protein orosomucoid (alpha1-acid glycoprotein) is needed to maintain the high capillary permselectivity required for normal homeostasis. It is not known how the protein executes its action, but it seems to contribute to the charge barrier. Moreover, recent studies suggest that the endothelial glycocalyx is essential for the charge barrier. The main site of orosomucoid synthesis is the liver, but we wanted to explore the possibility that orosomucoid was synthesized in endothelial cells. Primary cultures of human microvascular endothelial cells (HMVEC) from dermal tissue were established. Human liver cells were used as positive controls, and total RNA was prepared from both cell types. Reverse transcription-polymerase chain reaction (RT-PCR) was performed and demonstrated orosomucoid expression. After RT-PCR, the identities of the PCR products were confirmed by sequencing. RNase protection assay performed on total RNA from the HMVEC confirmed the results from the RT-PCR, i.e., orosomucoid mRNA is expressed by endothelial cells. Synthesis of orosomucoid in both liver and endothelial cells was demonstrated by immunoprecipitation. In conclusion, endothelial cells normally produce orosomucoid, which is essential for capillary charge selectivity. We suggest that orosomucoid exerts its effect by interacting with other components of the endothelial glycocalyx.

Capillary Permeability↗
PubMed2000

Orosomucoid has a cAMP-dependent effect on human endothelial cells and inhibits the action of histamine.

The plasma protein orosomucoid (alpha(1)-acid glycoprotein) has previously been shown to constitute a critical component of the capillary barrier. The protein has also been suggested to act as an anti-inflammatory mediator in a diversity of experimental situations. Recently we reported that orosomucoid is synthesized by the microvascular endothelial cells per se. In the present study, the effects of orosomucoid on primary cultures of human umbilical vein endothelial cells (HUVEC) were studied using the Cytosensor microphysiometer. We found that 1) orosomucoid (0.01 g/l) increased the metabolic activity of HUVEC as reflected by the increased acidification rate of +14 +/- 1%; 2) pretreatment with 0.5 mM 8-bromo-cAMP for 20 min markedly and reversibly inhibited the effect of orosomucoid, whereas 8-bromo-cGMP did not; 3) histamine elicited a dose-dependent response that was abolished by pretreatment with either cAMP or cGMP; and finally, 4) pretreatment of HUVEC for 6 min with orosomucoid (0.01 g/l) inhibited the action of histamine. In summary, this is the first report demonstrating that orosomucoid affects human endothelial cells and that it does so by using cAMP as a second messenger. This provides an explanation for previous findings of anti-inflammatory effects of the protein and shows that orosomucoid affects the endothelium during both normal and pathophysiological conditions.

2,4-Dinitrophenol↗
PubMed1989

Urinary orosomucoid excretion rate in patients with non-insulin-dependent diabetes mellitus.

Urinary excretion rate and clearance of alpha 1-acid glycoprotein (orosomucoid), a major serum glycoprotein which is more anionic (pI 2.7) than albumin (pI 4.7) were measured by RIA in timed overnight urine samples from non-insulin-dependent diabetic patients with different urinary albumin excretion rate and from healthy controls. The 50th percentiles of urinary orosomucoid excretion rate in patients with normo-, micro-, and macroalbuminuria were larger than those in healthy controls. Urinary excretion rate and clearance of orosomucoid increased in parallel with increase in albumin excretion rate in diabetic patients with an albumin excretion rate of more than 10 micrograms/min. On the basis of their levels of urinary orosomucoid excretion, patients with normoalbuminuria of less than 10 micrograms/min could be divided into two groups, one with a normal and the other with an elevated urinary orosomucoid excretion rate. The findings suggest that kidneys of diabetic patients with an albumin excretion rate of more than 10 micrograms/min are unable to distinguish the difference in pI between albumin and orosomucoid, and that a subgroup with an elevated orosomucoid excretion rate may be present among diabetics with normoalbuminuria.

Adult↗