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)

Marked sensitivity to proteolytic degradation results in the loss of multiple antioxidant properties of ceruloplasmin (CP), the multicopper oxidase of mammalian plasma. In this study, gel filtration of virtually pure CP (purity 99.7%) yielded complexes of this protein. Subjecting the complexes to SDS-free PAGE revealed other proteins along with CP. These were identified as matrix metalloproteinases (MMP-2 and MMP-12) by means of tryptic fragment mass spectrometry. Electrophoretic bands corresponding to MMP-2 (72 and 67 kDa) and MMP-12 (22 kDa) displayed gelatinase activity. The identified proteinases contained heparin-binding motifs inherent in the complex-forming partners of CP, such as lactoferrin, myeloperoxidase, and serprocidines. Therefore, admixtures of MMPs can be efficiently eliminated from CP preparations by chromatography on heparin-Sepharose as proposed previously.
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PMID:Identification of complexes formed by ceruloplasmin with matrix metalloproteinases 2 and 12. 1996 22

The study was focused on the detection of changes in serum and tumor metal-containing proteins in animals during development ofdoxorubicin-resistant phenotype in malignant cells after 12 courses of chemotherapy. We found that on every stage of resistance development there was a significant increase in content of ferritin and transferrin proteins (which take part in iron traffick and storage) in Walker-256 carc'inosarcoma tissue. We observed decreased serumferritin levels at the beginning stage of the resistance development and significant elevation of this protein levels in the cases withfully developed resistance phenotype. Transferrin content showed changes opposite to that offerritin. During the development of resistance phenotype the tumor tissue also exhibited increased 'free iron' concentration that putatively correlate with elevation of ROS generation and levels of MMP-2 and MMP-9 active forms. The tumor non-protein thiol content increases gradually as well. The serum of animals with early stages of resistance phenotype development showed high ceruloplasmin activity and its significant reduction after loss of tumor sensitivity to doxorubicin. Therefore, the development of resistance phenotype in Walker-256 carcinosarcoma is accompanied by both the deregulation of metal-containing proteins in serum and tumor tissue and by the changes in activity of antioxidant defense system. Thus, the results of this study allow us to determine the spectrum of metal-containing proteins that are involved in the development of resistant tumor phenotype and that may be targeted for methods for doxorubicin sensitivity correction therapy.
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PMID:METALLOPROTEINS DURING DEVELOPMENT OF WALKER-256 CARCINOSARCOMA RESISTANT PHENOTYPE. 2625 44