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

1. Synthetic polymers of l-prolyl-l-prolylglycine of defined chain length, (Pro-Pro-Gly)(n), were found to be substrates for the enzyme protocollagen-proline hydroxylase, with optimum chain length n=5. Boiling the polymer (Pro-Pro-Gly)(15) increased its activity as a substrate but had no effect on (Pro-Pro-Gly)(5). 2. Protection of both or one of the N- and C-terminal groups made (Pro-Pro-Gly)(3) a better substrate, and collagenase digestion of hydroxylated tert.-pentyloxy-carbonyl-(Pro-Pro-Gly)(3) benzyl ester indicated that the central prolyl residues were the major points of hydroxylation. 3. The results suggest that the long-chain peptides are optimum substrates but that a triple-stranded structure is inhibitory for hydroxylation.
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PMID:The enzymic hydroxylation of protocollagen models. 431 Oct 63

The first method for the qualitative and quantitative evaluation of extracellular and intracellular protease activities responsible for degradation of newly synthesized collagen is described. In a double incubation method, underhydroxylated collagen chains (protocollagen) serve as substrate for protease extract and then for the indicator enzyme, 4 prolyl hydroxylase. It was possible to characterize at least four types of protocollagen sites sensible to these proteases. The microsomal fraction of chick embryo liver contained a protease active on protocollagen and whose activity was similar to that of purified human synovial collagenase.
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PMID:A method for the measurement and characterization of protease activities responsible for extracellular or intracellular degradation of collagen precursors. 609 44

Lysyl oxidase and collagenase activities were measured in experimental acute and chronic liver injury in mice and rats, and correlated with collagen synthesis and accumulation. Acute liver injury was induced in mice and rats by a single dose of carbon tetrachloride given by gavage, and also in mice by a single injection of murine hepatitis virus. Chronic liver injury was induced in rats by repeated injections of carbon tetrachloride. Elevated plasma glutamic oxaloacetic transaminase levels, increased hepatic prolyl hydroxylase activity, and increased synthesis of collagen-bound hepatic hydroxyproline occurred in animals with acute as well as with chronic liver injury. However, only chronic liver injury appeared to be associated with fibrosis, increased collagen-bound hydroxyproline content, increased hepatic lysyl oxidase and collagenase activities, as well as with increased serum lysyl oxidase activity. These data suggest that lysyl oxidase and collagenase may play an important role in the collagen accumulation associated with hepatic fibrosis.
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PMID:Lysyl oxidase and collagenase in experimental acute and chronic liver injury. 611 72

The effect of 17 beta-estradiol (E2) on the biosynthesis of collagen in cultured bovine aortic smooth muscle cells was explored. Cells treated with various concentrations of the hormone for 14 days following subcultivation were subjected to growth studies. The cultures were also evaluated for [14C]hydroxyproline formation, the presence of collagenase-susceptible protein, prolyl hydroxylase activity, and procollagen types. There were no effect of E2 on the growth of these cells. At 10(-8) M E2, the hydroxylation of proline when compared to control cultures was reduced by 25-30%; however, little difference in extractable prolyl hydroxylase activity or total [14C]proline incorporation into protein was observed. The effect on collagen synthesis appears to be dose dependent over concentrations of E2 ranging from 10(-6) to 10(-12) M when measured by collagenase susceptibility. Procollagen typing on diethylaminoethylcellulose displayed reduced amounts of procollagen type I and type III fractions as well as other collagenous components. More importantly, however, the ratio of these two procollagen types were also altered. Similar results were obtained from the medium or cell layer. It is concluded that aortic smooth muscle cells cultured in the presence of 17 beta-estradiol display a decreased production of collagen in addition to altering the ratio of type I to type III procollagen fractions produced.
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PMID:Effects of 17 beta-estradiol on the biosynthesis of collagen in cultured bovine aortic smooth muscle cells. 626 9

Polysomes were isolated from calcified and matrix-containing tissues, such as rat calvaria, rat chondrosarcoma and chick embryos. The method of isolation involves preliminary swelling of the tissues in hypotonic buffer containing heparin and cycloheximide. After homogenization, differential centrifugation is used to separate membrane-bound and non-bound polysomes. Each fraction is rehomogenized in the presence of detergent (Triton X-100) and potassium ions (0.25M). Polysomes are harvested by centrifugation through sucrose cushions in the continued presence of high levels of potassium ions and heparin. Total, non-bound, and membrane-bound polysomes prepared in this manner are equally active in protein synthesizing activity in an heterologous cell-free system. The distribution between non-bound and membrane-bound polysomes in the 12 day old chick embryo is 43 and 57 per cent respectively. Sucrose gradient profiles of polypeptide chains on polysomes labeled in organ culture correlate well with the protein synthetic activity of the isolated polysomes. Much of the protein synthetic activity is devoted to collagen. Polysomal fractions obtained from sucrose gradients show preferential incorporation of 3H-proline and nearly 60 per cent of trichloroacetic acid precipitable material is susceptible to collagenase digestion. Products of synthesis are also substrates for collagen specific enzyme, prolyl hydroxylase. The method described in this communication overcomes the inherent difficulties in obtaining active polysomes from calcified and matrix-containing tissues.
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PMID:Isolation and partial characterization of active polysomes from calcified and matrix-containing tissues. 627 Oct 84

In confluent human skin fibroblasts maintained in 0.5% serum-supplemented medium. L-ascorbate specifically stimulated the rate of incorporation of labeled proline into total collagenase-sensitive protein, without changing the specific activity of the intracellular free proline. This influence of ascorbate reached a maximum at 30 microM and continued for at least 4 days, resulting in a 4-fold increase. The ascorbate effect occurred in cells at both confluent and subconfluent densities and was evident at all serum concentrations from 0.5-20%. The effect was independent of duration of the radioactive pulse between 2-6 h. D-Ascorbate, D-isoascorbate, and L-dehydroascorbate also stimulated collagen synthesis but at considerably higher concentrations, i.e., 250-300 microM. The stimulation of collagen synthesis by ascorbate and its analogs was accompanied by a decline in prolyl hydroxylase activity and a rise in lysyl hydroxylase activity; again L-ascorbate was found to be most effective. Dimethyltetrahydropterine and L-lactate failed to produce these effects.
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PMID:Collagen synthesis in cultured human skin fibroblasts: effect of ascorbic acid and its analogs. 630 3

The contribution of collagen degradation, as measured by collagenase activity, to the accumulation of collagen during hepatotoxic fibrogenesis was examined using a carbon tetrachloride rat model. Both active and inactive enzyme forms were determined with the inactive form quantitated following activation by limited trypsin digestion of the liver homogenate. The rate of collagen biosynthesis was monitored by quantitating hepatic prolyl hydroxylase activity and accumulation of collagen. In one study CCI4 was administered twice weekly, i.p. (0.2 mL, 33% v/v in light mineral oil) for sixteen weeks, with animals sacrificed every two weeks. Histologic examination of liver sections and serum alanine transaminase levels indicated a progressive necrosis and fibrosis which was confirmed by the increase in hepatic hydroxyproline content from 0.303 to 4.84 micrograms/mg wet wt. tissue. Prolyl hydroxylase activity increased in a time dependent manner to a maximum of 3.7 X control. This increase was accompanied by a large increase in both active collagenase (15.0-40.8 mU/g protein) and latent collagenase activity (69.8-191.7 mU/mg protein). These increases were maintained through the transition to irreversible fibrosis. The increase in active collagenase activity was positively correlated with collagen content. A second short term CCI4 treatment study confirmed a transient alteration in the active to latent collagenase ratio early in the fibrotic process. These results demonstrate the dynamic changes in hepatic collagenase levels and indicate that the fibrotic lesion is not dependent on decreased collagenase levels for collagen accumulation.
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PMID:Hepatic collagenase activity during carbon tetrachloride induced fibrosis. 630 97

Based on the finding that prolyl hydroxylase, a key enzyme in collagen biosynthesis, is a constituent of the hepatic parenchymal cell, we have suggested that the hepatocyte may synthesize collagen (Exp. Cell Res. 123: 269-279, 1979). We now report that, consistent with this idea, collagen formation has been detected in primary nonproliferating cultures of isolated rat hepatocytes prepared from either normal liver or regenerated liver four days after partial hepatectomy. The characteristics of the radiolabeled collagen formed in two-day old cultures incubated for 24 hours in the presence of either [3H]-proline or [35S]-cystine were its resistance to pepsin and its susceptibility to degradation by highly purified, protease-free bacterial collagenase. The presence of fibroblasts in the hepatocyte cultures was excluded as an explanation for these results because we detected no type I collagen, a universal product of the cultured fibroblast. The initial low rates of synthesis of collagen relative to total cellular protein (0.1-0.4 percent) increased dramatically upon continued incubation of the cells reaching 0.31 and 0.81 percent in nine-day old cultures of normal or regenerated hepatocytes, respectively. This change was accompanied by the synthesis of an additional 100,000 molecular weight from of collagen, possibly type I or A, B. Morphologically, the hepatocytes progressively flattened and overlapped adjacent cells with time in culture. However, their identify as hepatocytes was confirmed by the fact that synthesis of fibrinogen, a liver-specific function, was maintained above initial levels throughout the experiment. We conclude that synthesis of collagen is a constitutive function of the hepatocyte. This function is linked to hepatocyte replication, is subject to phenotypic change in culture, and may be important in the pathogenesis of hepatic fibrosis or cirrhosis.
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PMID:Collagen synthesis by the hepatocyte: studies in primary cultures of parenchymal cells from adult rat liver. 734 23

The effect of cadmium (Cd) on bone collagen synthesis was assessed in organ cultures of embryonic femur by measuring the incorporation of [3H]-proline(Pro) into collagenous-digestible protein (CDP) using purified bacterial collagenase. Cd produced a decrease when [3H]Pro ws incorporated in CDP. There was little alteration in the hydroxylation of [3H]Pro to [3H]hydroxyproline(Hyp) in CDP of Cd-treated bone. An accumulation of underhydroxylated collagen and a decrese in the activity of prolyl hydroxylase (EC 1.14.11.2) in Cd-treated bone was not observed. These reslts indicated that the inhibitory effect of Cd on collagen synthesis was largely due to inhibition of collagenous peptide synthesis without inhibition of its hydroxylation.
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PMID:Inhibitory effect of cadmium on collagenous peptide synthesis of embryonic chick bone in tissue culture. 740 91

The effect of colchicine and vinblastine on collagenase, lysyl oxidase and prolyl hydroxylase activities as well as on collagen cross-linking and types of this protein in bleomycin induced lung fibrosis in rats was investigated. Both colchicine and vinblastine diminish bleomycin-induced changes in the above-mentioned enzyme activities as well as collagen cross-linking and normalize type I/type III collagen ratio.
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PMID:The effect of colchicine and vinblastine on bleomycin-induced lung fibrosis in rats. 754 Mar 48


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