Disease relevance of Orm1

• We have studied the glucocorticoid-mediated accumulation of alpha 1-acid glycoprotein (AGP) in mRNA in HTC rat hepatoma cells [1].
• In contrast to the well-characterized primary response of mouse mammary tumor virus, in vitro transcription assays in isolated nuclei show that the rate of transcription of the AGP gene is high even in the absence of hormone [1].
• Expression of the alpha-1 acid glycoprotein (AGP) gene (agp) is activated by a key transcription factor, AGP/enhancer-binding protein (AGP/EBP, commonly called C/EBP beta), in the liver during the acute-phase response [2].
• CONCLUSIONS: Although AGP transcription was similar in mild and fulminant sepsis, double-puncture CLP increased the binding activity of the p50 homodimer relative to binding of the p50/p65 NF-kappaB heterodimer [3].
• RESULTS: FCA injection led to the development of an acute inflammatory response evidenced by paw edema and increased alpha-1-acid glycoprotein (AGP) and total-nitrite (NOx) plasma concentrations [4].

High impact information on Orm1

• Fetuin and orosomucoid, two glycoproteins with terminal sialic acid on their oligosaccharide chains, did not block the action of the conjugate [5].
• Thus, the molecular mechanism for agp gene activation may involve the interaction of AGP/EBP and TFIIB mediated by coactivator Nopp140 [2].
• The 142-bp cytokine response element of the rat alpha 1-acid glycoprotein (AGP) gene is a complex of several additively contributing regulatory sequences [6].
• To identify the regulatory sequence that is responsive to the peptide hormones, different lengths of the AGP gene 5'-flanking DNA were linked to the chloramphenicol acetyltransferase gene and then assayed for hormone-inducible chloramphenicol acetyltransferase gene expression in transiently transfected HepG2 cells [7].
• The steroid and peptide hormones stimulate expression of the AGP gene synergistically as well as independently [7].

Chemical compound and disease context of Orm1

• AGP/EBP(LAP) expressed in rat hepatoma cells interacts with multiple promoter sites and is necessary for maximal glucocorticoid induction of the rat alpha-1 acid glycoprotein gene [8].
• In the rat hepatoma (HTC) cell line, transcription of the alpha 1-acid glycoprotein (AGP) gene is prominently stimulated by dexamethasone [9].
• alpha-1-Acid glycoprotein (AGP), which is produced in the mammalian liver and secreted into the blood-stream, is regulated by steroid hormones and by mediators of the acute phase response [10].
• In groups of rats with polyarthritis studied on the 14th and 21st day there was no difference of arthritic index, volume of paw or orosomucoid concentration in neither low nor high dose metronidazole as compared to the control groups [11].

Biological context of Orm1

• Furthermore, three of these potential glycosylation sites are in a region that exhibits extensive amino acid sequence conservation, suggesting that this region may be important for the biological function of alpha 1-AGP [12].
• The complete nucleotide sequence of rat alpha 1-acid glycoprotein (alpha 1-AGP) mRNA has been determined from cloned double-stranded cDNA [12].
• We show that in rat primary hepatocytes, 9-cis retinoic acid and all-trans retinoic acid increase AGP gene expression at the transcriptional level [13].
• The AGP gene region between 120 and 42 base pairs upstream from the start site of transcription was found to mediate maximal dexamethasone induction of CAT enzyme levels [14].
• This result was unexpected because this region does not contain sequence homologies to known glucocorticoid receptor-binding sites and those AGP gene regions that lay further upstream and were homologous to other glucocorticoid receptor-binding sites were inactive in the CAT assay [14].

Anatomical context of Orm1

• Tubular epithelial cell structure (actin cytoskeleton) and cell-cell interaction (tight-junction architecture) were completely preserved in AGP-treated mice [15].
• The effects of AGP are thought to be mediated by fucose groups expressed on the AGP protein inhibiting neutrophil infiltration [15].
• In this study, we purify and identify a C/EBP family member, AGP/EBP(LAP), present in the rat hepatoma cell line HTC (JZ.1) which also binds to the C/EBP recognition sites in this region [8].
• Spontaneous AGP secretion by alveolar macrophages was increased 4-fold in patients with interstitial lung involvement compared with that in controls [16].
• In contrast to the high levels of AGP mRNA in the decidua only very low levels were detected in fetal liver and visceral yolk sac, and there was only a small increase in the levels in maternal liver [17].

Associations of Orm1 with chemical compounds

• To define the dexamethasone-responsive genetic element, we isolated and tested AGP gene sequences for the ability to confer glucocorticoid induction to the bacterial chloramphenicol acetyltransferase (CAT) gene in L cells [14].
• AGP gene expression remained inducible by IL-1, IL-6, and phenobarbital (PB) in GH-treated hepatocytes [18].
• Acute phase mediators and glucocorticoids increase the synthesis of the acute phase protein alpha 1-acid glycoprotein, also known as orosomucoid, by inducing the hepatic level of its mRNA [19].
• In vitro binding of IgG.125I-BSA complexes by isolated hepatocytes was effectively competed by asialofetuin, asialo-orosomucoid, galactose, and N-acetylgalactosamine, but was unaffected by fetuin, orosomucoid, ovalbumin, mannan, or mannose [20].
• Moreover, the induction of beta-globin mRNA directed by the AGP promoter is inhibited by concurrent treatment with cycloheximide, thereby suggesting that the requirement for protein synthesis is mediated through 5'-flanking sequences [21].

Other interactions of Orm1

• METHODS: Plasma levels of the acute-phase proteins interleukin-6 (IL-6), alpha1-acid glycoprotein (orosomucoid), fibrinogen, and alpha1-inhibitor3 were quantified in 3 strains of rats during the development and progression of disease: DA and LEW.1F, which are susceptible to arthritis, and E3, which is resistant [22].
• Use of radioactive glucosamine in the perfused rat liver to prepare alpha 1-acid glycoprotein (orosomucoid) with 3H- or 14C-labelled sialic acid and N-acetylglucosamine residues [23].
• Four anionic proteins were studied, namely albumin (Alb), orosomucoid (Oro), ovalbumin (Ova), and anionic horseradish peroxidase (aHRP), together with the neutral polymer Ficoll [24].
• In adjuvant arthritis, haptoglobin, seromucoid, and chiefly orosomucoid serum levels were generally very sensitive to anti-inflammatory agents such as phenylbutazone and pyridinol carbamate, and to immunosuppressive agents such as L-asparaginase [25].
• Immunoglobulins and albumin, alpha-1-antitrypsin, transferrin, and orosomucoid were present [26].

Analytical, diagnostic and therapeutic context of Orm1

• Liver AGP was then isolated by immunoprecipitation [27].
• Endocytosis of desialylated orosomucoid by hepatocytes isolated from regenerating liver following two-thirds hepatectomy is reduced by 80% and returns to normal when regeneration is substantially complete [28].
• AGP transcription was assessed with transcription elongation analysis, intrahepatic IL-1beta, and TNF-alpha abundance by using immunohistochemistry, and serum IL-1beta was assessed by using ELISA [3].
• Immunological determination of alpha-1-acid glycoprotein (AGP) revealed a marked increase after laparotomy and a linear relationship was found between the plasma AGP concentration and the binding capacity of high-affinity binding site for propranolol in plasma (r = 0.961, P less than .001) [29].
• We examined the association between alpha(1)-acid glycoprotein (AGP), all-trans-retinol (retinol), and albumin concentrations in a longitudinal animal model of IL-6-induced inflammation [30].

References