Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.11.2 (prolyl hydroxylase)
 1,814 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The etiology of pulmonary fibrosis remains unclear, and at present there are no definite biochemical markers of its activity. We measured serum and BALF levels of type III procollagen N-terminal peptide (P-III-P), prolyl hydroxylase (PH), and laminin P1 in patients who had undergone radiotherapy for malignant neoplasms, and investigated their value as biochemical markers in a model of pulmonary fibrosis. The following results were obtained: 1) Patients with abnormal liver function had significantly higher serum P-III-P levels and showed a tendency to have higher serum PH levels. If P-III-P or PH are to be used as markers of pulmonary fibrosis, the effect of liver function must be taken into consideration; however, no significant difference was detected with respect to laminin P1 levels. 2) Serum P-III-P levels were significantly elevated by radiotherapy. 3) Laminin P1 levels rose in a similar manner to P-III-P levels after radiotherapy, but no significant change was detected. 4) In most cases, the levels of all markers in BALF were below the threshold of detection, nevertheless all three markers were elevated in a patient who developed diffuse radiation pneumonitis during radiotherapy. Increases in the lymphocyte count were found in BALF of this patient. 5) BALF hyaluronic acid levels were negative in the 3 cases assayed. 6) A significant correlation between P-III-P and laminin P1 in serum was shown, but no significant correlations could be found between the other combinations of markers in serum. Thus it appears that serum P-III-P and laminin P1 are valid biochemical markers of pulmonary fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Type III procollagen N-terminal peptide (P-III-P, prolyl hydroxylase (PH), and laminin P1 levels in serum and BALF of radiotherapy patients]. 132 Jul 8

Serum levels of several markers for liver fibrosis were measured utilizing three groups of human subjects related with schistosomiasis mansoni in northeast Brazil; (1) 20 Schistosoma mansoni egg-positives, who have never been administered with anti-schistosomal drugs, (2) 29 egg-negative inhabitants in the endemic area of schistosomiasis, and (3) 23 egg-negative Japanese immigrants in the non-endemic area. None of these sera were positive for antibody to the surface antigen of human hepatitis B (HBs) and circulating HBs antigen. There was no significant difference in the serum levels of N-terminal peptide of procollagen type-III between the egg-positive subjects and either of the egg-negative Brazilian or Japanese immigrants, whereas the mean value of serum laminin significantly increased in the egg-positive subjects. A significantly higher concentration of serum immunoreactive beta-subunit of prolyl 4-hydroxylase (IR beta PH) was also observed in the egg-positive subjects only in comparison with that of the egg-negative Brazilian. Serum laminin and IR beta PH concentrations of the egg-positive subjects did not correlate with the absorbance of enzyme-linked immunosorbent assay (ELISA) which utilized crude antigens isolated from schistosome adults or eggs. No significant difference in these two parameters was observed between two subgroups of the egg-negative Brazilian or Japanese immigrants divided according to the serological data by ELISA. These findings suggest that serum laminin and IR beta PH levels are worth further evaluation for their usefulness as the marker for liver fibrosis in schistosomiasis.
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PMID:Elevation of laminin and beta-subunit of prolyl 4-hydroxylase in the sera of human subjects with Schistosomiasis mansoni. 255 32

In this second part, clinical aspects of connective tissue metabolism in the liver will be described and two main aspects considered. The first is the possibility to monitor the activity of fibrosis by the use of metabolites and enzymes of connective tissue metabolism. In recent studies the qualification for this purpose of enzymes such as procollagen prolyl hydroxylase and lysosomal N-Acetyl-beta-glucosaminidase and the N-terminal peptide of procollagen type III has been tested. The serum activities or concentrations of these substances in patients with chronic active liver diseases increase in due relation to the histologically estimated activity of liver fibrosis. The second aspect deals with therapeutic approaches to fibrosis in the liver by using connective tissue specific agents. So far none of the antifibrotic substances such as proline analogues, colchicine, lathyrogens and penicillamine has been used in longer-term antifibrotic treatment.
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PMID:Connective tissue components of the normal and fibrotic human liver. II. Clinical aspects. 704 67

The vital hydroxylation of peptidyl proline residues in collagens and protein with collagen-like amino acid sequences is catalyzed by the tetrameric enzyme prolyl 4-hydroxylase (P4-H). We have previously detailed [John et al. (1993) EMBO J. 12, 1587-1595] the redox-dependent assembly of the catalytically important alpha-subunit (64 kDa) in a cell-free system containing endogenous beta-subunits (PDI, 60 kDa). To identify the origin of this redox-dependent assembly, we have now shown directly by an electrophoretic mobility shift assay that the assembled wild-type protein possesses at least one intramolecular disulfide bond. We also analyzed five alpha-subunit mutants that have single Cys to Ser mutations in one of the five Cys residues present in the wild-type protein and found that (i) subunits mutated at Cys150 or Cys511 formed intramolecular disulfide bonds, whereas subunits mutated at Cys276, Cys293, or Cys486 did not, (ii) mutation of Cys276, Cys293, or Cys486 led to a large reduction in alpha-beta complex formation, (iii) subunits mutated at Cys276, Cys293, Cys486, or Cys511 were recognized by an antiserum raised against an alpha-subunit C-terminal peptide which failed to recognize the assembled wild-type subunit or the assembled subunit mutated at Cys150, and (iv) the assembled complexes fractionated in a similar position to the purified protein on sucrose gradients whereas the assembly-defective mutants formed higher molecular weight aggregates or complexes with other proteins. On the basis of these results, we propose that P4-H alpha-subunits possess an intramolecular disulfide bond between Cys276 and Cys293 that is essential for alpha-beta complex formation.
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PMID:Prolyl 4-hydroxylase: defective assembly of alpha-subunit mutants indicates that assembled alpha-subunits are intramolecularly disulfide bonded. 794 11

C-terminal peptide of procollagen I, N-terminal peptide of procollagen III, collagen IV and serum prolyl hydroxylase were measured in 100 patients with cirrhosis and 71 patients with noncirrhotic chronic liver disease. Patients with cirrhosis had significantly higher mean values of prolyl hydroxylase, collagen IV, N-terminal peptide of procollagen III and C-terminal peptide of procollagen I as compared to noncirrhotic patients. This difference was maintained for collagen products even after stratification for alcohol intake, although all markers of fibrosis were higher in alcoholics. Stepwise logistic regression analysis showed that collagen IV, and N-terminal peptide of procollagen III were independently associated with cirrhosis. Receiver-operating characteristic (ROC) curves showed that collagen IV and N-terminal peptide of procollagen III perform more efficiently than C-terminal peptide of procollagen I and prolyl hydroxylase in identifying cirrhosis.
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PMID:A comparison of four serum markers of fibrosis in the diagnosis of cirrhosis. 913 47

The transmissible spongiform encephalopathies are characterized by conversion of a host protein, PrP(C) (cellular prion protein), to a protease-resistant isoform, PrP(Sc) (prion protein scrapie isoform). The importance of the highly flexible, N-terminal region of PrP has recently become more widely appreciated, particularly the biological activities associated with its metal ion-binding domain and its potential to form a poly(L-proline) II (PPII) helix. Circular dichroism spectroscopy of an N-terminal peptide, PrP(37-53), showed that the PPII helix is formed in aqueous buffer; as it also contains an Xaa-Pro-Gly consensus sequence, it may act as a substrate for the collagen-modifying enzyme prolyl 4-hydroxylase. Direct evidence for this modification was obtained by mass spectrometry and Edman sequencing in recombinant mouse PrP secreted from stably transfected Chinese hamster ovary cells. Almost complete conversion of proline to 4-hydroxyproline occurs specifically at residue Pro44 of this murine protein; the same hydroxylated residue was detected, at lower levels, in PrP(Sc) from the brains of scrapie-infected mice. Cation binding and/or post-translational hydroxylation of this region of PrP may regulate its role in the physiology and pathobiology of the cell.
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PMID:Post-translational hydroxylation at the N-terminus of the prion protein reveals presence of PPII structure in vivo. 1103