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)

125I-Pituitary adenylate cyclase-activating polypeptide (PACAP) 1-38 is able to bind a factor in human plasma, which can be displaced by unlabelled PACAP 1-38 and PACAP 28-38 but not by the other biologically active form, PACAP 1-27. Likewise, 125I-PACAP 28-38 binds this plasma factor, whereas 125I-PACAP 1-27 does not. Apparent Kd values were measured to be 12.0+/-1.3 and 3.4+/-1.5 nM for PACAP 1-38 and PACAP 28-38, respectively, using a competition assay with 125I-PACAP 28-38. Purification of the PACAP 1-38-binding factor from human blood was made by ethanol precipitation of serum followed by Ni2+-chelating and anion-exchange chromatography. A 120-kDa band on SDS/PAGE, as well as some proteolytic products, was blotted on to PVDF membrane and their N-terminal amino acid sequences determined. In combination with a mass-spectrometric fingerprinting of a tryptic digest of the 120-kDa band, this PACAP 1-38-binding factor was identified as ceruloplasmin. Purified commercial ceruloplasmin shows identical mobility on SDS/PAGE to the PACAP 1-38-binding factor and the same binding characteristics to PACAP 1-38, 1-27 and 28-38, using the same amount of ceruloplasmin as was expected to be found in the human plasma. Furthermore, the ability of plasma to bind 125I-PACAP 1-38 or 28-38 disappeared when ceruloplasmin was immunoprecipitated from plasma with rabbit anti-human ceruloplasmin Ig.
 ...
PMID:Identification of pituitary adenylate cyclase-activating polypeptide1-38-binding factor in human plasma, as ceruloplasmin. 1039 82

When lactoferrin (LF) and myeloperoxidase (MPO) are added to ceruloplasmin (CP), a CP-LF-MPO triple complex forms. The complex is formed under physiological conditions, but also in the course of SDS-free PAGE. Polyclonal antibodies to both LF and MPO displace the respective proteins from the CP-LF-MPO complex. Similar replacement is performed by a PACAP38 fragment (amino acids 29-38) and protamine that bind to CP. Interaction of LF and MPO with CP-Sepharose is blocked at ionic strength above 0.3 M NaCl and at pH below 4.1 (LF) and 3.9 (MPO). Two peptides (amino acids 50-109 and 929-1012) were isolated by affinity chromatography from a preparation of CP after its spontaneous proteolytic cleavage. These peptides are able to displace CP from its complexes with LF and MPO. Both human and canine MPO could form a complex when mixed with CP from seven mammalian species. Upon intravenous injection of human MPO into rats, the rat CP-human MPO complex could be detected in plasma. Patients with inflammation were examined and CP-LF, CP-MPO, and CP-LF-MPO complexes were revealed in 80 samples of blood serum and in nine exudates from purulent foci. These complexes were also found in 45 samples of serum and pleural fluid obtained from patients with pleurisies of various etiology.
 ...
PMID:Interaction of ceruloplasmin, lactoferrin, and myeloperoxidase. 1751 5

Pituitary adenylate cyclase-activating polypeptide (PACAP) is an inhibitor of megakaryopoiesis and platelet function. Recently, PACAP deficiency was observed in children with nephrotic syndrome (NS), associated with increased platelet count and aggregability and increased risk of thrombosis. To further study PACAP deficiency in NS, we used transgenic Tg(cd41:EGFP) zebrafish with GFP-labeled thrombocytes. We generated two models for congenital NS, a morpholino injected model targeting nphs1 (nephrin), which is mutated in the Finnish-type congenital NS. The second model was induced by exposure to the nephrotoxic compound adriamycin. Nephrin RNA expression was quantified and zebrafish embryos were live-screened for proteinuria and pericardial edema as evidence of renal impairment. Protein levels of PACAP and its binding-protein ceruloplasmin were measured and GFP-labeled thrombocytes were quantified. We also evaluated the effects of PACAP morpholino injection and the rescue effects of PACAP-38 peptide in both congenital NS models. Nephrin downregulation and pericardial edema were observed in both nephrin morpholino injected and adriamycin exposed congenital NS models. However, PACAP deficiency was demonstrated only in the adriamycin exposed condition. Ceruloplasmin levels and the number of GFP-labeled thrombocytes remained unchanged in both models. PACAP morpholino injections worsened survival rates and the edema phenotype in both congenital NS models while injection with human PACAP-38 could only rescue the adriamycin exposed model. We hereby report, for the first time, PACAP deficiency in a NS zebrafish model as a consequence of adriamycin exposure. However, distinct from the human congenital NS, both zebrafish models retained normal levels of ceruloplasmin and thrombocytes. We further extend the renoprotective effects of the PACAP-38 peptide against adriamycin toxicity in zebrafish.
 ...
PMID:Pituitary adenylate cyclase-activating polypeptide (PACAP) in zebrafish models of nephrotic syndrome. 2875 37