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)

Lysyl oxidase catalyzes the crosslinking of collagen and elastin. Lysyl oxidase activity was measured and localized in rat liver during the evolution of hepatic fibrosis induced by CCl4. Enzyme activity measured with DL-[6-3H]-lysine-labeled collagen substrates in liver and plasma increased sharply after approximately 3 wk of injection, reached a maximum at 6 wk, and then decreased. The increase in activity correlated histologically with early connective tissue septa formation, and the magnitude of increase was significantly greater than that found for the intracellular collagen biosynthetic enzymes protocollagen prolyl hydroxylase and lysyl hydroxylase. Indirect immunofluorescence studies showed that lysyl oxidase was present in association with collagen in the extracellular space. However, it was not possible to correlate the distribution pattern with a particular liver cell type. These observations suggest that serial measurements of lysyl oxidase activity in liver or plasma may be useful for correlating changes in connective tissue formation with histologic connective tissue deposition.
 ...
PMID:Biochemical and immunochemical study of lysyl oxidase in experimental hepatic fibrosis in the rat. 2 18

Liver protocallagen proline hydroxylase activity (PPH activity) was determined in patients with various liver diseases, CCl4-induced liver fibrosis rats and cholin deficiency (tcd) fatty liver rats. The following results were obtained: Liver PPH activity in patients with chronic hepatitis was higher than that in patients with acute hepatitis, while the activity in patients with liver cirrhosis was much higher than that in patients with chronic hepatitis. The activity was higher in patients with chronic active hepatitis than in those with chronic inactive hepatitis. Patients with active and progressive liver cirrhosis were found to have an especially high PPH activity, in whom the activity reflected well the degree of liver fibrosis. Even though fibrosis in persistent hepatitis was almost negligible or slight, the degree of liver PPH activity in persistent hepatitis was similar to that in liver cirrhosis. Liver PPH activities in CCl4-induced liver fibrosis rats and CD fatty liver rats elevated proportionally to the lapse of time. Whilst liver PPH activity in rats of CD fatty liver without fibrosis in 23 to 31 weeks after the start of the experiment was slightly lower than that in rats of CD fatty liver with fibrosis. But liver PPH activity of the former was considerably higher than that of control rats.
 ...
PMID:Liver protocollagen proline hydroxylase in human liver diseases and experimental liver fibrosis. 19 57

A significant increase in the activity of prolyl hydroxylase, in the relative collagen synthesis and in the hydroxyproline content was observed in the liver of rats treated for five weeks with CCl4 when compared to control liver. Five weeks after the suspension of the treatment, the activity of prolyl hydroxylase and the relative collagen synthesis returned to normal, but the hydroxyproline content of the liver of the CCl4-treated animals remained significantly higher than that of the controls. These findings suggest that an impairment in the mechanisms responsible for the resorption of the scar tissue could account for the accumulation of collagen within the parenchyma in liver fibrosis.
 ...
PMID:Collagen metabolism in the liver of normal and carbon tetrachloride treated rats. 23 Aug 65

In the present study we evaluated the protective activity of pyridoxol L,2-pyrrolidon-5 carboxylate (metadoxine) against CCl4 intoxication in rats, especially in relation to liver fibrosis. After 6 consecutive weeks of CCl4 treatment, the animals developed liver fibrosis and inflammation as revealed by histological analysis which also included semiquantitative scoring of these features. In addition the serum levels of the immunoreactive prolyl hydroxylase (SIRPH), an enzyme involved in the hydroxylation of the procollagen molecule, were significantly higher (44.2 +/- 16.3 micrograms/ml; P less than 0.005) in this group of animals than in controls (26.1 +/- 8.06). On the contrary, animals treated with CCl4 + metadoxine (200 mg/kg i.p.) had less severe liver fibrosis and normal SIRPH levels (21.5 +/- 14.6). These data suggest that metadoxine may be an effective pharmacological tool for preventing the progression of liver disease in rats exposed to CCl4 to cirrhosis.
 ...
PMID:Pyridoxol L,2-pyrrolidon-5 carboxylate prevents active fibroplasia in CCl4-treated rats. 131 Aug 10

Changes in serum and hepatic levels of immunoreactive prolyl hydroxylase (IRPH) as well as cellular localization of the enzyme were studied in 2 models of hepatic fibrosis, which was induced in male rats either by subcutaneous administration of CCl4 (Group A) or by intraperitoneal injection of porcine serum (Group B). Hepatic fibrosis appeared at the 8th week in Group A and at the 12th week in Group B, and liver cirrhosis developed at the 16th week in both models. Although tissue contents of hydroxyproline (HP) and IRPH increased in both models, only HP levels correlated with the degree of fibrosis. Serum IRPH levels and serum asparate aminotransferase (AST) activities increased, showing a significant positive correlation, in group A, whereas both remained in a control range in Group B. Moreover, in another model which received a single intraperitoneal injection of CCl4, serum IRPH showed a marked increase and then a rapid decrease in parallel with the change in serum AST. Immunohistochemical analysis also showed a difference between the two fibrosis models: in group A, IRPH was positive mainly in parenchymal cells in the peripheral zone of the pseudolobulus, while in group B the staining was diffuse. These results indicate that the elevation of serum IRPH is, at least in part, due to the parenchymal cell damage, and that IRPH levels should be carefully evaluated when being used as a parameter to estimate the activity of fibrogenesis in the liver.
 ...
PMID:Changes in serum and hepatic levels of immunoreactive prolyl hydroxylase in two models of hepatic fibrosis in rats. 165 96

S 0885 and HOE 077 inhibit CCl4-induced liver fibrosis in rats, as shown by significantly reduced hydroxyproline content of the liver and improved liver histology. Mortality of drug-treated animals is significantly diminished. Serum collagen parameters correlate well with the hydroxyproline content of the liver and can be used as noninvasive markers for the fibrotic process. HOE 077 is a proinhibitor, which by itself does not inhibit prolyl 4-hydroxylase. HOE 077 is well absorbed from the gastrointestinal tract. It is taken up by rat liver and is converted to the active metabolites. At a concentration of 1 mM, HOE 077 does not affect collagen synthesis in human fibroblasts, bovine chondrocytes and chicken calvaria. At therapeutic doses the compound does not reduce collagen content of kidney, lung, aorta, femur epiphysis, skin and tendon of the rat, validating the high specifity of the liver selective prodrug/inhibitor conversion. From animal experiments, a human daily dose of 0.5-1 g can be extrapolated.
 ...
PMID:Beneficial effects of inhibitors of prolyl 4-hydroxylase in CCl4-induced fibrosis of the liver in rats. 166 66

A study was conducted to examine the inhibitory effect of acyclic retinoid (polyprenoic acid) on the development of hepatic fibrosis induced by CCl4 in rats. Oral administration of the compound brought about a significant reduction in both serum and tissue levels of immunoreactive prolyl hydroxylase, a key enzyme of collagen formation. The result indicated that the rate of collagen synthesis in the liver was decreased which was consistent with histological findings. Acyclic retinoid also decreased both AST and ALT activities in serum, demonstrating the reduction in hepatic parenchymal damage. This cytoprotective effect on parenchymal cells may be related, at least in part, to inhibition of hepatic fibrosis. No significant side effects were observed, despite a long-term administration of the acyclic retinoid. The present findings suggest the potential scope of therapy of hepatic fibrosis by retinoid.
 ...
PMID:Inhibitory effect of acyclic retinoid (polyprenoic acid) on hepatic fibrosis in CCl4-treated rats. 216 74

We developed a competitive enzyme-immunoassay for serum type IV collagen peptide as a marker of fibrogenesis, and examined the relationship between serum type IV collagen peptide and hepatic disorder in CCl4-treated rats. The rats were treated for 8 weeks and signs of liver damage began to appear from about week 2. With the progression of these signs to liver fibrosis, type IV collagen increased in the fibrous septa and especially in the perisinusoidal walls, where the increase was manifested as development of a real basement membrane beneath the sinusoidal endothelial cells. In CCl4-treated rats, serum type IV collagen peptide significantly increased with the progression of liver fibrosis. When CCl4 administration was stopped, the collagen peptide rapidly decreased without any rebound rise. An intimate relationship was found between the production of serum type IV collagen peptide and liver prolyl hydroxylase activity and the amount of collagen deposited in the liver. These results suggest that serum type IV collagen peptide will be a useful biochemical marker for the early detection of fibrogenesis in the liver.
 ...
PMID:Increased serum type IV collagen peptide in carbon tetrachloride-treated rats. 271 35

Malotilate is a new drug suggested for use in chronic liver diseases. It is shown here to prevent liver damage caused by CCl4. The concomitant administration of malotilate with CCl4 significantly decreased hydroxyproline accumulation in the liver, liver prolyl 4-hydroxylase and liver and serum galactosylhydroxylysyl glucosyltransferase activities. However, it had no effect on the daily urinary hydroxyproline excretion or the hydroxyproline content of the skin, liver or lungs in normal young growing rats. It also had no specific inhibitory effect on hydroxyproline synthesis or secretion in fibroblast cultures, and did not affect the amount of procollagen-alpha 1(I)-specific mRNAs in these cultures. Thus it seems to have no direct inhibitory effect on collagen metabolism. In addition to inhibition of liver collagen accumulation, malotilate was also able to prevent the development of morphological changes in the liver such as focal necrosis, fatty infiltration and inflammatory changes. It also normalized almost completely the standard liver-function tests. It is possible that malotilate may prevent excessive collagen deposition by inhibiting the inflammation caused by CCl4-induced liver damage.
 ...
PMID:Preventive effect of malotilate on carbon tetrachloride-induced liver damage and collagen accumulation in the rat. 282 40

Monospecific antibodies directed against type I, type III collagens, and prolyl hydroxylase were used to clarify the process of liver fibrosis after CCl4 intoxication in rats by the direct immunoperoxidase method. In acute CCl4 intoxication, fat-storing cells (FSCs) were increased in number in the areas of necrosis around the central veins. These FSCs exhibited intense positive stainings for type I, type III collagens, and prolyl hydroxylase in well-developed rough endoplasmic reticula and Golgi apparatus. This was the direct evidence that the collagens formed after CCl4 intoxication are produced by FSCs. In chronic CCl4 intoxication, increased FSCs in and around the fibers also contained strong immunoreactive materials of both collagens and prolyl hydroxylase mainly in the rough endoplasmic reticula. These collagens were also present in the Golgi apparatus and vesicles close to the cytoplasmic membrane, demonstrating the exocytic process of collagen formation of FSCs. In contrast, faint immunoreactions of both collagens were found in the rough endoplasmic reticula and Golgi apparatus of hepatocytes during the process of fibrosis. These findings indicate that FSCs play an important role in fibrogenesis after acute and chronic CCl4 intoxication in the rat.
 ...
PMID:Collagen production in fat-storing cells after carbon tetrachloride intoxication in the rat. Immunoelectron microscopic observation of type I, type III collagens, and prolyl hydroxylase. 284 91


1 2 Next >>