Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.16.3.1 (ceruloplasmin)
 5,074 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stimulation of the immune system results in a series of metabolic changes that are antagonistic toward growth. Monokines, including interleukin-1, tumor necrosis factor, and interleukin-6, are released from cells of the monocyte-macrophage lineage after recognition of immunogens. They appear to mediate homeorhetic response, which alters the partitioning of dietary nutrients away from growth and skeletal muscle accretion in favor of metabolic processes which support the immune response and disease resistance. These alterations include 1) decreased skeletal muscle accretion due to increased rates of protein degradation and decreased protein synthesis; 2) increased basal metabolic rate resulting in increased energy utilization; 3) use of dietary amino acids for gluconeogenesis and as an energy source instead of for muscle protein accretion; 4) synthesis by the liver of acute phase proteins; 5) redistribution of iron, zinc, and copper within the body due to the hepatic synthesis of metallothionein, ferritin, and ceruloplasmin; (6) impaired accretion of cartilage and bone; and 7) release of hormones such as insulin, glucagon, and corticosterone. These monokines also influence the differentiation of cells. Tumor necrosis factor suppresses the differentiation of myoblasts and adipocytes whereas the chicken monokine myelomonocytic growth factor induces the differentiation of granulocytes.
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PMID:Monokines in growth and development. 171 68

The acute-phase response to inflammatory stimuli, characterized by increased synthesis of acute-phase proteins (APP), is often accompanied by changes in the glycosylation patterns of some of these proteins. While expression of APP genes in hepatocytes is regulated by monokines, mechanisms governing changes in glycosylation are not known. Exposure of human hepatoma cell line Hep 3B to conditioned medium from LPS-activated human monocytes and to medium from the keratocarcinoma cell line COLO-16 led to increased synthesis of alpha 1 proteinase-inhibitor and ceruloplasmin and to alterations of their glycosylation patterns similar to those seen in human serum in various inflammatory states. IL-1, tumor necrosis factor, and hepatocyte stimulating factor I increased synthesis of ceruloplasmin without alterations in the pattern of its glycosylation. These findings demonstrate that altered glycosylation seen in plasma in some inflammatory states can be explained by the effects of monokines on glycosylation in hepatocytes and that gene expression and glycosylation of some APP during the acute-phase response may be regulated by different mechanisms.
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PMID:Monokines regulate glycosylation of acute-phase proteins. 243 35

The synthesis of all the major acute phase plasma proteins is stimulated in rat hepatoma and primary cultures of hepatocytes by three, structurally and functionally distinct groups of hormones: 1) hepatocyte-stimulating factors (HSF) and interleukin-6 (IL-6); 2) interleukin-1 (IL-1) and tumor necrosis factor (TNF); and 3) glucocorticoids. Each plasma protein gene requires a specific combination of these 3 hormone types for maximal expression. One set of acute phase proteins, including alpha 2-macroglobulin, alpha 1-antichymotrypsin ( = contrapsin), cysteine protease inhibitor ( = thiostatin), alpha 1-antitrypsin, ceruloplasmin and fibrinogens are predominantly regulated by the keratinocyte-derived HSF-III/-II or IL-6, while a second set of proteins, including alpha 1-acid glycoprotein (AGP), haptoglobin and complement C3 are predominantly regulated by keratinocyte-derived HSF-I, IL-1 or TNF. In conjunction with the above peptide hormones, glucocorticoids synergistically enhance the stimulated expression of most, but not all, acute phase proteins. An exceptionally strong synergy between HSF (or IL-6), IL-1 and glucocorticoids is noted for the activation of the AGP gene. To elucidate the molecular mechanisms of regulation, we have identified the cis-acting genetic elements through which all these hormones control the transcriptional activity of the AGP gene. It appears that acute phase activates a specific nuclear binding protein in the rat liver that interacts with the peptide hormone responsive element located 5 kb upstream of the transcriptional start site.
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PMID:Regulation of acute phase protein genes by hepatocyte-stimulating factors, monokines and glucocorticoids. 248 67

The degree of complement activation produced by hydrogen peroxide was estimated by the inhibition of serum homolytic activity (% IHA). Sera from patients with systemic lupus erythematosus and psoriasis vulgaris were resistant to hydrogen-peroxide-mediated complement activation. %IHA negatively correlated with ceruloplasmin level or catalase activity in systemic lupus erythematosus sera, but did not correlate with transferrin level. The addition of free metal ions, FeCl2 or CuCl2, promoted hydrogen-peroxide-mediated complement activation. These results suggest that hydroxyl radical is involved in complement activation and that the factors responsible for the insensitivity of pathological sera to H2O2 are catalase and ceruloplasmin in the sera. Human skin fibroblasts generate superoxide and tumor necrosis factor enhanced it, but interleukin-1 beta inhibited it. Normal serum cultured with fibroblasts for 24 h showed complement activation via catalase-inhibitable process, suggesting that hydrogen peroxide has an important role in fibroblast-mediated complement activation. It is speculated that fibroblasts and complement activation by oxygen radicals have an important role in inflammation and subsequent tissue damage at the site of skin lesion.
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PMID:Possible role of H2O2-mediated complement activation and cytokines-mediated fibroblasts superoxide generation on skin inflammation. 255 Feb 83

We have investigated the effect of cytokines, including interleukin-6 (Il-6), interleukin-1 alpha (Il-1 alpha), and tumor necrosis factor-alpha (TNF-alpha), on the inducible expression of cytochrome P450s (CYP) CYP1A1, CYP1A2, and CYP3A4 in human hepatocytes in primary culture. The ability of these cultures to mimic the acute phase response when stimulated with cytokines was evaluated using immunoblotting to measure the production of albumin, ferritin, fibrinogen, and ceruloplasmin. The cytokines exhibited specific patterns of action on the production of these proteins. Albumin was depressed by all the cytokines. In contrast to Il-6 and Il-1 alpha, TNF-alpha reduced the production of fibrinogen and ceruloplasmin but stimulated the production of ferritin. When cells were treated with the CYP inducer alone, large increases in the expression of CYP1A1 and CYP1A2 by beta-naphthoflavone and of CYP3A4 by rifampicin were observed at messenger RNA (mRNA) and protein levels, by ribonuclease protection and immunoblotting, respectively. When the cells were treated with the inducer plus cytokines, the induction of mRNA was greatly reduced. Again, specific patterns of action were revealed: Il-6 had the most potent effect on CYP3A4, whereas TNF-alpha was the most potent with CYP1A genes. In all cases, changes at the protein levels paralleled changes at the mRNA levels. In cells preinduced with beta-naphthoflavone or rifampicin, the decay with time of the levels of the CYP1A2 or CYP3A4 proteins, after the removal of the inducer, was not affected by cytokines. We conclude that cytokines strongly repress the inducibility of CYP1As and CYP3A4 genes at a transcriptional or a posttranscriptional level, but affect neither the rate of translation of CYP mRNAs nor the rate of degradation of the CYP proteins in these cultures.
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PMID:Differential effects of cytokines on the inducible expression of CYP1A1, CYP1A2, and CYP3A4 in human hepatocytes in primary culture. 755 64

Metallothionein (MT) synthesis induced by the inflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF), was studied in vivo. Administration of recombinant human IL-6 or TNF to rats caused the acute phase responses including rapid decreases in plasma zinc (Zn), and increases in plasma copper (Cu) and ceruloplasmin. Hepatic concentration of MT-I, one of MT isoforms, began to increase within 3 h after the injection of IL-6 or TNF. In IL-6-treated rats, MT-I concentration in liver reached a maximum level at 12 h and decreased with a transient rebound, whereas, in TNF-treated rats, a high level of MT-I lasted for about 48 h. MT-II, the other MT isoform, was induced more than MT-I in liver by both cytokines. MT-I was also induced in lung and heart by TNF, but little by IL-6. The data suggest that IL-6 may be responsible for MT synthesis in liver, whereas TNF may be responsible not only in liver but also in lung and heart. Furthermore plasma concentration of MT did not always reflect the enhanced concentration of MT by TNF and IL-6 in liver, suggesting involvement of many factors influencing plasma MT levels. The interrelation between IL-6 and TNF for MT synthesis has also been discussed.
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PMID:Differential induction of metallothionein synthesis by interleukin-6 and tumor necrosis factor-alpha in rat tissues. 818 7

Twelve Holstein bull calves (6 to 8 wk of age) were used to determine the influence of supplemental dietary Cr on ACTH, cortisol, and immune responses of calves experimentally inoculated with bovine herpesvirus-1 (BHV-1). Calves supplemented with Cr received 3 mg Cr/d (Chromium, n = 6) of a high-Cr-yeast product. Following 53 d of treatment, all calves were fitted with jugular catheters, and blood samples were collected every 4 h into tubes containing ETDA. Twenty-four hours later, all calves were inoculated intranasally with BHV-1 (1 x 10(7) plaque-forming units in each naris). Serial blood collection continued at 4-h intervals for 6 d. Plasma was harvested, immediately frozen in liquid nitrogen, and stored at -20 degrees C. Individual rectal temperatures and urine samples were collected at the same time each day. Rectal temperatures were elevated (P < .05) on d 2, 3, 4, and 5 but were not affected by Cr treatment. Treatment with Cr did not affect secretion of ACTH, cortisol, or plasma tumor necrosis factor-alpha, although clear circadian variation in ACTH and cortisol occurred. No differences were detected in the concentrations of trace minerals excreted daily in the urine, lymphocyte proliferative response to mitogen stimulation, and neutrophil bactericidal function. The acute phase proteins, ceruloplasmin and fibrinogen, also were not affected by treatment or viral challenge. These data suggest the Cr supplementation using high-Cr yeast (3 mg/d) did not alter stress responses of calves experimentally inoculated with BHV-1.
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PMID:Supplemental dietary chromium does not influence ACTH, cortisol, or immune responses in young calves inoculated with bovine herpesvirus-1. 902 69

To identify a possible acute phase response during the steady state of sickle cell disease, we estimated the serum alterations of acute phase proteins, beta2-microglobulin (beta2M), kappa and lambda light chains, interleukins (ILs) and tumor necrosis factor-alpha (TNFalpha) in 21 patients. Increased concentrations of C-reactive protein (CRP) were found in 5 patients, alpha-1-acid-glycoprotein (AGP) in 3, alpha-1-antitrypsin (AAT) in 8, ceruloplasmin (CER) in 2, alpha-2-macroglobulin (AMG) in 14 and decreased haptoglobin (HPT) and transferrin (TFR) in 11 and 9, respectively. Increased beta2M was found in 10 patients and kappa and lambda light chains in 11. IL-1beta, IL-2, IL-4, IL-10 and TNFalpha were not detected in any of the patients. However, significantly increased values of IL-6 and sIL-2r were found. This study has demonstrated increased serum levels of some of the acute phase proteins in patients during the steady state of sickle cell disease. This may be a result of a subclinical vaso-occlusion which in turn leads to a covert inflammatory response. Cytokines, and in particular IL-6, produced after this response, seem to be responsible for the high levels of acute phase proteins in the steady state of this disease.
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PMID:Acute phase proteins and interleukins in steady state sickle cell disease. 968 92

Twenty-four male Holstein calves were used to determine the effects of dietary Cu and Mo on performance, Cu status, and immune function of calves. Calves were fed a milk replacer that was deficient in Cu for 8 wk and then were randomly assigned after weaning to one of four treatments: 1) control (no supplemental Cu or Mo), 2) 10 mg of Cu (from CuSO4)/kg of dry matter (DM) (Cu diet), 3) 5 mg of Mo (from Na2MoO4)/kg of DM (Mo diet), or 4) 5 mg of Cu (from CuSO4) and 5 mg of Mo (from Na2MoO4)/kg of DM (Cu + Mo diet). The basal diet was a semipurified diet that contained approximately 1.1 mg of Cu and 1.1 mg of Mo/kg of DM. Calves fed the Cu and Mo diets gained weight more efficiently than those fed the control and Cu + Mo diets during the 112-d study. By d 84 of the study, calves fed the Cu diet had higher plasma Cu concentrations and plasma ceruloplasmin activities than did calves fed the other three diets and had higher liver Cu concentrations on d 136. Plasma and liver Cu concentrations did not differ among calves fed the control, Mo, and Cu + Mo diets. At d 112, activity of Cu-Zn superoxide dismutase was lower in calves fed the Mo diet than in calves fed the Cu diet. Serum total antibodies to porcine erythrocytes (primary response) were lower in calves fed the Mo diet than in calves fed the Cu diet at 7, 14, and 21 d postinoculation. Production of tumor necrosis factor and interleukin-1 by isolated peripheral blood monocytes was not significantly affected by treatment. Although no differences were apparent in plasma or liver Cu concentrations among calves fed the control, Mo, and Cu + Mo diets, calves fed the Mo diet had a more severe Cu deficiency based on depressed humoral immune response and superoxide dismutase activity.
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PMID:Effects of dietary copper and molybdenum on copper status, cytokine production, and humoral immune response of calves. 989 Dec 74

Our objectives were to study the value of different proteins in the serum and ascitic fluid and assess their potential in discriminating between malignant and nonmalignant ascites in a model that could be developed to aid clinical diagnosis. In all, 57 different measurements (30 in serum and 27 in ascitic fluid) including erythrocyte sedimentation rate, number of white blood cells, cytokines, interleukin-1a (IL-1a), IL-1b, IL-2, IL-6, IL-8, tumor necrosis factor-alpha, immunoglobulins (IgG, IgA, IgM), complement factors C3 and C4, acute-phase proteins such as alpha1-acid glycoprotein, alpha2-macroglobulin, alpha1-antitrypsin, haptoglobin, C-reactive protein, ferritin, ceruloplasmin and transferin, were performed in 61 patients with ascites (25 with malignant exudates, 13 with nonmalignant exudates, and 23 with transudates). Patients with sepsis were excluded. Correlation tests and one-way ANOVAs were used for comparisons between different groups. Discriminant analyses were used to assess the significance of each parameter in the differentiation process. Correct classification of 100% of cases required the use of all 57 ascitic fluid measurements in the model, which was not considered practical in clinical diagnosis. Discriminant analysis showed that five ascitic fluid measurements-total protein, LDH, TNF-alpha, C4, and haptoglobin-were sufficient for a model to correctly classify 89% of cases. Cross-validation showed that 70% of unknown cases were correctly classified using this model. In conclusion, we have shown that five easily taken protein measurements in the ascitic fluid can differentiate to a large extent between cases with ascites and have proposed a relatively simple statistical model with these parameters that could be developed to be extremely useful in the clinical setting.
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PMID:Discrimination between malignant and nonmalignant ascites using serum and ascitic fluid proteins in a multivariate analysis model. 1074 24


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