Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Insufficiencies of the circulatory system and increasing transport losses in pigs as well as analogies with respect to atherosclerosis of men and swine were the motives for a broad statistical investigation of important characteristics of the circulatory system in a big population of female German landrace pigs, fattened as progeny groups under identical conditions in a testing station and slaughtered at 100 kg weight. As the most essential results, highly significant seasonal and genetical influences on several traits are to be mentioned, and some meaningful correlations between them: Plasma cholesterol, ceruloplasmin and hematocrit showed markedly lower levels in the summer and increased values in the cold season; the thickness of the intima (aorta and arteria pulmonalis) was quite distinctly greatest in the spring, this phenomenon being almost exactly paralleled by augmented amounts of copper and iron in the aortic wall. Increased heart weights were again found in the cold, decreased ones in the warm seasons. On average, bigger hearts and vessels were accompanied by higher elastin contents of the aorta, but these contents stood in very significant negative correlation to the ash content and the amounts of certain mineral components (Ca, Mg and P) of the vessel wall, especially to the ash percentage of the elastic fibers. This indicates that calcifying and mineralizing processes in the wall obviously take place at the cost of the elastic components. The estimation of heritabilities in half and full sibs revealed with h2 = 60% high henetic influences on the elastin content of the aorta and equally so on the ash percentage of elastic fibers. Future investigations must correlate these findings with direct measurements of biomechanical and rheological properties of the vessels.
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PMID:[The exogenous and genetic components of some vessel wall characteristics in the pig (author's transl)]. 122 Jun 64

Inflammatory aneurysms of the abdominal aorta (IAA) comprise 10-15% of all aortic aneurysms (AA) but their aetiology and pathogenesis are obscure. Destruction of mural elastin is a prominent feature of IAA, and both increased elastolysis and decreased inhibition of elastolysis have been implicated. In order to study these factors, we have examined the peripheral blood of three groups of patients; 15 with inflammatory aortic aneurysms (IAA), 61 with simple aortic aneurysms (SAA) and 35 with aorto-iliac occlusive disease (OD). In all cases, alpha-1-anti-trypsin (A-1-AT), alpha-2-macroglobulin (A-2-MG), elastase inhibitory activity (E.I.A.), elastase-anti-trypsin complex, C-reactive protein (CRP), caeruloplasmin (CP) and plasma viscosity were measured. Patients with IAA had a significantly higher plasma viscosity (Mann-Whitney, p less than 0.05), E.I.A. (Mann-Whitney, p less than 0.01) and levels of A-1-AT, CRP, CP and elastase/anti-trypsin complex (Mann-Whitney, all p less than 0.05) than patients in the other two groups. There was no difference in the levels of A-2-MG between any of the groups. This study refutes the theory that reduced inhibition of elastase activity predisposes to the formation of SAA. In patients with IAA, raised marker levels indicate ongoing destruction of elastin, and suggest a difference in pathogenesis between IAA and SAA. The study also suggests that IAA are highly active metabolically, as opposed to the more degenerative SAA.
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PMID:Metabolic activity in inflammatory and non-inflammatory aneurysms of the abdominal aorta. 137 41

The authors describe a patient who presented from birth on a severe involvement of connective tissues with pathological fractures, lack of auricular cartilage, hyperlaxity of fingers and cutis laxa with deep folds, all suggestive of derangements of collagen and elastin. Hypothermia at 24 hours of age should have already indicated the possibility of Menkes' syndrome. From the 3rd month on, the patient presents a neurological deterioration and a myoclonic epilepsy which is resistant to treatment. Craniocerebral tomodensitometry revealed, with time, a cerebral atrophy and subdural hematomas. Angiodysplasia of a coronary artery was seen at cardiac echocardiography. Undetectable levels of serum copper and ceruloplasmin, and an increased uptake of copper by fibroblasts in vitro confirmed the diagnosis of Menkes' syndrome. Electron microscopy of a skin biopsy disclosed a desmosomal anomaly in the epidermis. Desmosomes stay apart suggesting an alteration of the interdesmosomal cement.
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PMID:[Menkes disease. Report of a case with pronounced involvement of connective tissues and changes in epidermal desmosomes]. 270 74

Copper's role in connective tissue is linked to the enzyme lysyl oxidase. From a biochemical perspective, copper is a cofactor for the enzyme and a determinant of its activity in connective tissues. Lysyl oxidase catalyses a post-translational oxidation of certain lysine and hydroxylysine residues. The peptidyl aldehydes so formed become active centres for the formation of cross-links in collagen and elastin. Less well understood is how copper controls the steady-state activity of lysyl oxidase; the enzyme fails in copper deficiency. Giving copper to a deprived animal increases lysyl oxidase activity in aortic tissue. Such activation in vivo appears to require caeruloplasmin. Suspending aortic tissue in a copper-enriched growth medium also activates lysyl oxidase provided that tissue structure is kept intact. Activation in vitro occurs with the binding of copper to a large-molecular-weight component, presumably the enzyme. Binding will not occur if protein synthesis is blocked. These studies clearly show that the synthesis of mature elastin and collagen can be controlled by the availability of copper. They further suggest that transport of copper to aortic tissue and its engagement to lysyl oxidase are linked to the synthesis or lysyl oxidase, an extracellular carrier, or both.
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PMID:Copper and the synthesis of elastin and collagen. 611 May 24

When leukocyte lysosomal extracts are used as a source of elastase and are combined with a fraction of plasma containing sufficient alpha 1-protease inhibitor (alpha 1-Pi) to inhibit all but 30 to 40% of the elastase amidase activity, elastolysis occurs at 69% of the rate of the uninhibited elastase controls (0.125 M NaCl; pH, 6.5). Proteolysis of elastin requires the presence of NaCl. At pH 8.6, elastolysis is decreased to 30 to 40% of free elastase controls by 1.0 M NaCl. At pH 6.5, on the other hand, elastolysis is increased to 83% of the control values by these higher NaCl concentrations. The activity of human leukocyte myeloperoxidase is optimal at pH 6 to 6.5 and at NaCl concentrations between 0.25 and 1.0 M. Purified myeloperoxidase, alpha 1-Pi, and elastase, in the presence of NaCl and hydrogen peroxide, can reproduce this phenomenon at pH 6.5, suggesting that the occurrence of elastolysis in lysosomal extract-plasma mixtures may in part be a result of the oxidative inactivation of alpha 1-Pi by myeloperoxidase present in the lysosomal extract. Human ceruloplasmin, the major antioxidant of plasma, inhibits this myeloperoxidase-dependent reaction, without interfering either with free elastase activity or with the appearance of activity in plasma-lysosomal extract mixtures at pH 8.6. The "antioxidant" activity of ceruloplasmin is inhibited by azide. These results suggest that antioxidants such as ceruloplasmin may be an important determinant of lung defense in persons chronically exposed to oxidants.
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PMID:Ceruloplasmin: plasma inhibitor of the oxidative inactivation of alpha 1-protease inhibitor. 628 6

Lysyl oxidase is a copper-dependent enzyme involved in extracellular processing of collagens and elastin. Although it is known that copper is essential for the functional activity of the enzyme, there is little information on the incorporation of copper. In the present study we examined the insertion of copper into lysyl oxidase using 67Cu in cell-free transcription/translation assays and in normal skin fibroblast culture systems. When a full-length lysyl oxidase cDNA was used as a template for transcription/translation reactions in vitro, unprocessed prolysyl oxidase appeared to bind copper. To examine further the post-translational incorporation of copper into lysyl oxidase, confluent skin fibroblasts were incubated with inhibitors of protein synthesis (cycloheximide, 10 microg/ml), glycosylation (tunicamycin, 10 microg/ml), protein secretion (brefeldin A, 10 microg/ml) and prolysyl oxidase processing (procollagen C-peptidase inhibitor, 2.5 microg/ml) together with 300 microCi of carrier-free 67Cu. It was observed that protein synthesis was a prerequisite for copper incorporation, but inhibition of glycosylation by tunicamycin did not affect the secretion of 67Cu as lysyl oxidase. Brefeldin A inhibited the secretion of 67Ci-labelled lysyl oxidase by 46%, but the intracellular incorporation of copper into lysyl oxidase was not affected. In addition, the inhibition of the extracellular proteolytic processing of prolysyl oxidase to lysyl oxidase had minimal effects on the secretion of protein-bound 67Cu. Our results indicate that, similar to caeruloplasmin processing [Sato and Gitlin (1991) J. Biol. Chem. 266, 5128-5134], copper is inserted into prolysyl oxidase independently of glycosylation.
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PMID:Incorporation of copper into lysyl oxidase. 935 64

Turkey poults were inoculated at hatch with the "W" isolate of Bordetella avium. At 17 d of age, serum copper levels and ceruloplasmin activities were determined. The trachea and aorta were analyzed for collagen and elastin content in an attempt to relate these structural proteins to the clinical observations of tracheal ring distortion and cardiac dysfunction associated with bordetellosis. Serum copper levels and ceruloplasmin activity were elevated in the B. avium-infected poults and indicated enzyme activity sufficient for elastin and collagen cross-link formation. In the infected poults, crude elastin content was increased significantly (0.67% infected vs 0.59% control) in the trachea but not in the aorta (13.12% infected vs 12.68% control). However, collagen content in infected poults (69.7 hydroxyproline residues per 1,000 amino acid residues) was decreased in the trachea compared to the controls (97 hydroxyproline residues per 1,000 amino acid residues), whereas collagen and elastin cross-links (HLNL, hydroxy-lysinohydroxy-norleucine, moles per mole of collagen per 300 residues hydroxyproline) were increased in the trachea of infected poults (2.85 in infected vs 1.80 in control) and also increased (DHLNL, dihydroxy-lysinohydroxy-norleucine, moles/mole of collagen/300 residues hydroxyproline) in the aorta (0.49 in infected vs 0.39 in control) of infected poults. The differences in collagen and elastin content, in association with differences in the cross-linking, appeared to be the cause of tracheal collapse that is characteristic of B. avium infection and also may have an adverse influence on cardiovascular function.
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PMID:The effects of Bordetella avium infection on elastin and collagen content of turkey trachea and aorta. 983 39

We report a 7.5-year-old boy with loose translucent skin, aortic dilatation, hyperextensible veins, recurrent respiratory problems, pectus excavatum, arthralgias, lax joints, mild epiphyseal dysplasia, and umbilical and inguinal hernias. He also has developmental delay, progressive bilateral sensorineural hearing loss, an unusual facial appearance, terminal digit hypoplasia with unusual radiographic changes in some of the phalanges, glandular hypospadias, shawl scrotum, and undescended testes. Biochemical investigations, including electrophoresis of Types 1 and 3 procollagens and collagens, and quantification of serum copper and ceruloplasmin, are normal. Relative to age-matched control patients the electron micrographs of the boy's dermis show elastin fibers to be decreased in number, and abnormal in appearance, with a low matrix to microfibril ratio. The organ distribution of abnormalities and the nature of the findings suggest a connective tissue disorder. We contrast and compare this boy's phenotype to those of the classic connective tissue disorders. We conclude that he has cutis laxa with features that distinguish him from previously described types of cutis laxa.
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PMID:A boy with developmental delay, malformations, and evidence of a connective tissue disorder: possibly a new type of cutis laxa. 1270 60

An eight-week, 2 x 4 factorial rat experiment using two levels of dietary copper and four levels of dietary silicon was conducted to further delineate a previously observed silicon-copper interaction in which silicon appears to mimic copper in its effect on the composition of the aorta. Dietary copper concentrations were 1.4 (deficient) and 5.4 (adequate) mg/kg diet, and silicon concentrations were 5, 135, 270, and 540 mg/kg diet. Compared with the lowest level of silicon and copper, weight gains were 15.5% higher for rats fed 540 mg silicon/kg diet and 14.3% higher for those fed 5.4 mg copper/kg diet. The growth-promoting effects of silicon and copper were additive. Evidence that silicon elevated the copper status of copper-deficient rats includes an increase in packed-cell volume by 540 mg silicon/kg diet in the otherwise packed-cell volume-depressed, copper-deficient rats, accompanied by a trend toward higher hemoglobin values and lower relative heart weights. In the copper-adequate rats, evidence that 540 mg silicon/kg diet elevated their copper status includes a two-fold increase in the blood-plasma copper concentration, a three-fold increase in ceruloplasmin activity, and an increase in cardiac, renal, and hepatic copper concentrations. In addition, 540 mg silicon/kg diet resulted in higher aortic dry mass and aortic elastin content in both copper-deficient and copper-adequate rats. While dietary silicon concentrations of 135, 270, and 540 mg/kg diet were all effective in increasing aortic elastin in the copper-adequate rats, only 540 mg silicon/kg diet increased aortic elastin in the copper-deficient rats. These data indicate that some of the metabolic effects attributed to silicon may be manifested through a silicon-facilitated increase in copper utilization.
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PMID:Silicon facilitation of copper utilization in the rat. 1553 41

This study was designed to clarify the effects of D-penicillamine (DPA), a drug used for treatment of various pathological events, on lung elastin formation and maturation of the newborn in the perinatal period. The investigation was conducted on 20 newborn rats bred from 40 female and six male rats. DPA doses 400 mg kg(-1) day(-1) and physiological saline were given intraperitoneally (i.p) to experimental and control groups. To assess newborn maturation, their body and lung weights were determined. Serum Cu levels were measured by atomic absorption spectroscopy and ceruloplasmin (Cp) activities were measured spectrophotometrically. Newborn lung tissue elastin, desmosine (DES) and isodesmosine (IDES) levels were measured by HPLC. The results showed that DPA treatment caused loss of skin elasticity and reduction in body and lung weight in newborns of the experimental group. The serum Cu levels and Cp activity were found to be significantly lower in both maternal and newborn of the experimental groups compared with the control group. The lung DES, IDES and elastin values of newborns in the experimental group were decreased compared with the control group. In conclusion, our results indicate that 400 mg kg(-1) day(-1) DPA, a dose that is used in the treatment of Wilson's disease, rheumatoid arthritis and cystinuria, caused the retardation of newborn maturation, a decrease in DES-IDES cross-links and levels of lung elastin of offspring in the perinatal period. Another conclusion to be drawn from this study is that even low levels of Cu depletion due to DPA administration induces a change in cross-linking in lung elastin during the perinatal period.
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PMID:Effect of D-penicillamine on rat lung elastin cross-linking during the perinatal period. 1565 43


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