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)

Ceruloplasmin is a 132-kDa glycoprotein abundant in human plasma. It has multiple in vitro activities, including copper transport, lipid pro- and antioxidant activity, and oxidation of ferrous ion and aromatic amines; however, its physiologic role is uncertain. Although ceruloplasmin is synthesized primarily by the liver in adult humans, production by cells of monocytic origin has been reported. We here show that IFN-gamma is a potent inducer of ceruloplasmin synthesis by monocytic cells. Activation of human monoblastic leukemia U937 cells with IFN-gamma increased the production of ceruloplasmin by at least 20-fold. The identity of the protein was confirmed by plasmin fingerprinting. IFN-gamma also increased ceruloplasmin mRNA. Induction followed a 2- to 4-h lag and was partially blocked by cycloheximide, indicating a requirement for newly synthesized factors. Ceruloplasmin induction in monocytic cells was agonist specific, as IL-1, IL-4, IL-6, IFN-alpha, IFN-beta, TNF-alpha, and LPS were completely ineffective. The induction was also cell type specific, as IFN-gamma did not induce ceruloplasmin synthesis in endothelial or smooth muscle cells. In contrast, IFN-gamma was stimulatory in other monocytic cells, including THP-1 cells and human peripheral blood monocytes, and also in HepG2 cells. Ceruloplasmin secreted by IFN-gamma-stimulated U937 cells had ferroxidase activity and was, in fact, the only secreted protein with this activity. Monocytic cell-derived ceruloplasmin may contribute to defense responses via its ferroxidase activity, which may drive iron homeostasis in a direction unfavorable to invasive organisms.
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PMID:Induction of ceruloplasmin synthesis by IFN-gamma in human monocytic cells. 925 59

It was shown that ceruloplasmin, apart from the known oxidative conversion of dopamine into melanin, can also produce (DHI)-melanin from 5,6-dihydroxyindole and THP-melanin from tetrahydropapaveroline. Ceruloplasmin acts as an oxidase and the kinetic parameters for these oxidative reactions are reported. Since these ceruloplasmin-catalyzed reactions occur also at pH 7.4, they could have a significant physiological impact. This ceruloplasmin-oxidasic activity is enhanced by copper ions and inhibited by chelators, such as ethylenediaminetetraacetic acid (EDTA) and desferoxamine (DEF). Some possible implication of melanin production in blood are discussed.
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PMID:Production of melanins by ceruloplasmin. 958 47

The MmcO protein of Mycobacterium tuberculosis is a membrane-associated multicopper oxidase. Its natural substrate(s) and its role in pathogenesis are not well characterized. A recent report proposes that MmcO contributes to copper resistance in M. tuberculosis during infection. We have expressed and reconstituted the active enzyme from inclusion bodies in E. coli. MmcO exhibits maximal activity against the experimental substrate 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) or ABTS, at pH 4. The enzyme also exhibits ferroxidase activity at pH 4. Most notable was the finding that MmcO is able to scavenge the reactive oxygen species (ROS) generated by the xanthine/xanthine oxidase enzyme system. This ROS scavenging activity of MmcO was also evident against ROS generated by THP-1 cells. We propose that MmcO protects M. tuberculosis during infection against ROS attack in addition to providing copper resistance to the pathogen.
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PMID:The multicopper oxidase of Mycobacterium tuberculosis (MmcO) exhibits ferroxidase activity and scavenges reactive oxygen species in activated THP-1 cells. 3127 55