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

The respiratory burst of neutrophils generates oxygen radicals that can result in lipid peroxidation and may contribute to acute lung injury in the adult respiratory distress syndrome (ARDS). Because ceruloplasmin and transferrin are inhibitors of lipid peroxidation and may play a role in regulating tissue injury, antigen levels of ceruloplasmin and transferrin and ceruloplasmin oxidase levels were measured in the serum and bronchoalveolar lavage fluid (BALF) of ARDS patients (n = 28), patients at risk for ARDS (n = 22), and normal control subjects (n = 45). Serum ceruloplasmin levels were similar in ARDS (mean +/- SEM) (3.8 +/- 0.3 microM) and at-risk (3.3 +/- 0.4 microM) patients compared with control subjects (3.2 +/- 0.2 microM). Serum transferrin levels were decreased in ARDS (14.9 +/- 1.7 microM) and at-risk (20.4 +/- 1.7 microM) patients compared with normal control subjects (32.9 +/- 1.2 microM), and serum transferrin levels correlated with serum unsaturated iron binding capacity (UIBC). Ceruloplasmin was detected in only one of 38 normal BALF samples (0.002 +/- 0.002 microM) and two of 13 at-risk BALF samples (0.15 +/- 0.1 microM), yet it was present in 17 of 23 ARDS BALF samples (0.9 +/- 0.2 microM). Transferrin was also increased in ARDS BALF (5.4 +/- 1.1 microM) compared with at-risk (0.7 +/- 0.5 microM) and normal (0.4 +/- 0.1 microM) samples. Ceruloplasmin that was present in the BALF and serum samples had functional oxidase activity, and purified human ceruloplasmin inhibited hydroxyl radical formation by phorbol myristate acetate (PMA)-stimulated neutrophils.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ceruloplasmin and transferrin levels are altered in serum and bronchoalveolar lavage fluid of patients with the adult respiratory distress syndrome. 131 27

Phagocyte-mediated oxidant damage to vascular endothelium is likely involved in various vasculopathies including atherosclerosis and pulmonary leak syndromes such as adult respiratory distress syndrome. We have shown that heme, a hydrophobic iron chelate, is rapidly incorporated into endothelial cells where, after as little as 1 h, it markedly aggravates cytotoxicity engendered by polymorphonuclear leukocyte oxidants or hydrogen peroxide (H2O2). In contrast, however, if cultured endothelial cells are briefly pulsed with heme and then allowed to incubate for a prolonged period (16 h), the cells become highly resistant to oxidant-mediated injury and to the accumulation of endothelial lipid peroxidation products. This protection is associated with the induction within 4 h of mRNAs for both heme oxygenase and ferritin. After 16 h heme oxygenase and ferritin have increased approximately 50-fold and 10-fold, respectively. Differential induction of these proteins determined that ferritin is probably the ultimate cytoprotectant. Ferritin inhibits oxidant-mediated cytolysis in direct relation to its intracellular concentration. Apoferritin, when added to cultured endothelial cells, is taken up in a dose-responsive manner and appears as cytoplasmic granules by immunofluorescence; in a similar dose-responsive manner, added apoferritin protects endothelial cells from oxidant-mediated cytolysis. Conversely, a site-directed mutant of ferritin (heavy chain Glu62----Lys; His65----Gly) which lacks ferroxidase activity and is deficient in iron sequestering capacity, is completely ineffectual as a cytoprotectant. We conclude that endothelium and perhaps other cell types may be protected from oxidant damage through the iron sequestrant, ferritin.
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PMID:Ferritin: a cytoprotective antioxidant strategem of endothelium. 151 45

Bronchoalveolar lavage (BAL) fluid from normal subjects is a potent inhibitor of lipid peroxidation. This antioxidant activity (AOA) of BAL fluid is primarily due to the serum proteins transferrin and ceruloplasmin. In the adult respiratory distress syndrome (ARDS), there is an influx of protein-rich edema fluid into the alveolar space that may increase antioxidant activity and provide protection against further oxidant-mediated lung injury. To test this hypothesis, the AOA of BAL fluid was measured in patients with ARDS (n = 11) and normal subjects (n = 12). When compared with normal subjects, BAL fluid from ARDS patients had a significantly higher concentration of total protein (2,536.8 +/- 408.2 micrograms/ml vs. 77.3 +/- 7.0 micrograms/ml, P less than 0.005). When compared at several volumes, BAL fluid from ARDS patients was a more potent inhibitor of lipid peroxidation than BAL fluid from normals. In addition, when AOA was determined on equal milligram amounts of BAL fluid protein from ARDS patients and normal subjects, ARDS BAL fluid protein had a significantly higher AOA. Consistent with its higher AOA, ARDS BAL fluid contained increased concentrations of both transferrin (77.8 +/- 15.3 micrograms/ml vs. 2.78 +/- 0.3 micrograms/ml, P less than 0.05) and ceruloplasmin (36.5 +/- 5.6 micrograms/ml vs. 0.26 +/- 0.02 micrograms/ml, P less than 0.005) compared with normal subjects. The importance of both ceruloplasmin and transferrin in the enhanced AOA of ARDS BAL fluid was further demonstrated by studies that showed a significant decrement in AOA when the antioxidant functions of these two proteins were selectively blocked.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antioxidant activity of bronchoalveolar lavage fluid in the adult respiratory distress syndrome. 153 74

Crossed immunoelectrophoresis (X-IEP) revealed several abnormalities in serum proteins from patients with adult respiratory distress syndrome (ARDS), tuberculosis (TB), and cystic fibrosis (CF). The two quite different kinds of pulmonary disease, one acute (ARDS) and the other chronic (TB and CF) exhibited serum changes specific for each disease and abnormalities associated with inflammation and pathogenesis, in general. In ARDS sera, most proteins were extremely low, presumably due to leakage into the lungs through damaged tissue, while the acute-phase proteins, orosomucoid, alpha 1-antitrypsin, alpha 1-antichymotrypsin, and haptoglobin, were markedly high when compared to the overall protein pattern. The extremely high alpha 1-antichymotrypsin values were not seen in corresponding TB and CF sera. Numerous TB patients had elevated alpha 1-antitrypsin, alpha 1-antichymotrypsin, and haptoglobin, but only the alpha 1-antitrypsin population mean was significantly different from normal. Gc-globulin, ceruloplasmin, and beta-lipoprotein were higher and alpha 1-lipoprotein and inter-alpha-trypsin inhibitor lower than normal. All other quantitative serum changes were not statistically significant. Surprisingly, all TB patients belonged to the Gc-1-1 genotype in contrast to the Gc-1-1, Gc-1-2, Gc-2-2 polymorphisms of the other populations. CF homozygote sera revealed statistically significant increases in the acute-phase proteins, alpha 1-antitrypsin, alpha 1-antichymotrypsin, and haptoglobin, while orosomucoid, transferrin, IgA, and IgG tended to be higher than normal. The tendency for higher levels of transferrin indicated possible iron deficiency in some patients. In contrast, prealbumin, alpha 1-lipoprotein, and inter-alpha-trypsin inhibitor were significantly depressed in CF patients. CF heterozygotes shared the decrease of alpha 1-lipoprotein with the patients while exhibiting small but significant depressions of alpha 2-macroglobulin and IgG. Though not statistically significant, lowered concentrations of alpha 1-antitrypsin were evident for the heterozygotes.
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PMID:Protein abnormalities in adult respiratory distress syndrome, tuberculosis, and cystic fibrosis sera. 243 15

Ten adult patients (three male, age range, 15 to 67 years) with established ARDS were studied for serial changes in the proteinaceous antioxidant activities of their plasma. All had LISs in excess of 2.5 on admission to the study. Blood samples were taken as soon as possible after the diagnosis of ARDS, and from 10 patients at risk of developing ARDS. These were compared with healthy control subjects. Deoxyribose, phospholipids, and DNA were used as markers of damage in reactions generating inorganic and organic oxygen radicals and an oxo-iron species. The ability of plasma to inhibit such damage was expressed as antioxidant activity. This study does not address the clinical problem of why certain "at risk" patients develop ARDS, but rather the question of why some patients with established ARDS are better able than others to survive the disease. ARDS patients had transferrin levels that were significantly lower (1.76 +/- 0.13 gm/L) than those of normal controls (2.91 +/- 0.12 gm/L, p < 0.001), which decreased the ability of their plasma to protect phospholipid membranes and DNA against iron-stimulated free radical damage. The iron-oxidizing antioxidant properties of plasma were mainly dependent on the protein ceruloplasmin, concentrations of which were significantly higher in ARDS patients (0.387 +/- 0.04 gm/L) than in healthy controls (0.265 +/- 0.03 gm/L, p = < 0.05) or patients at risk of ARDS (0.24 +/- 0.04 gm/L, p = < 0.05). The iron-oxidizing (ferroxidase) antioxidant activities of plasma from ARDS patients, however, were similar to those of both control groups. Measurement of plasma ferroxidase activities confirmed that although more ceruloplasmin was present in the plasma of ARDS patients, enzyme activities were comparable to those of both control groups, which was suggestive of a loss of ceruloplasmin ferroxidase activity. Scavenging and radical-stimulating properties of plasma (devoid of iron-binding and iron-oxidizing properties) was partly dependent on protein thiol groups, which were lower in ARDS patients and in patients at risk of developing ARDS. Serial sample analysis revealed that ARDS patients showed substantial daily variations in biochemical parameters, implying that single time-point sampling may be unsuitable when studying these patients.
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PMID:Primary plasma antioxidants in adult respiratory distress syndrome patients: changes in iron-oxidizing, iron-binding, and free radical-scavenging proteins. 805 91