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Query: UNIPROT:P06889 (Mol)
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The tight-skin (Tsk) mouse is a genetic model of pulmonary emphysema linked to a deficiency of serum antielastase. In this mouse occurrence of connective tissue abnormalities in various organs (systemic scleroderma) has been reported. The aim of the present work was to study lung collagen synthesis and deposition in Tsk mice. No differences in the collagen synthesis rate and morphology at the ultrastructural level were found in Tsk mice at birth. At 2 months of age, a marked increase in collagen was observed within the alveolar septa. At this time, an increased lung collagen synthesis, assessed by determining prolyl hydroxylase activity and incorporation of radiolabeled proline, was found in Tsk mice with respect to control mice. However, due to the ongoing parenchymal destruction, the values of total lung collagen at 6 and 12 months of age were only moderately but significantly increased with respect to those observed at 2 months. As a consequence, a progressive accumulation of lung collagen fibers was observed in the residual septa. The increase in collagen deposition was accompanied by a relative increase in type I collagen. Although the data in the literature would suggest a genetic cause for the lung collagen change in Tsk mice, the data presented here indicate that the change in lung collagen metabolism may be a part of a remodeling process taking place after lung destruction.
Exp Mol Pathol 1992 Apr
PMID:Lung collagen synthesis and deposition in tight-skin mice with genetic emphysema. 158 42

Bleomycin damages cellular DNA and is a potent inducer of pulmonary fibrosis. It has been shown to act through a superoxide-mediated mechanism. We are interested in determining the biochemical mechanisms involved in fibrosis and in this preliminary study we have examined the temporal relationship between early biochemical events associated with DNA damage and fibrosis, in lungs of hamsters after administration of 0.75 unit of bleomycin. The activities of poly(ADP-ribose) synthetase, an enzyme associated with DNA repair, inducible superoxide dismutase (SOD) and prolyl hydroxylase as well as the tissue levels of NAD+ and hydroxyproline in the lung were determined. All three enzyme activities expressed as per milligram DNA or per lung, increased upon bleomycin treatment over the saline-administered controls. Lung poly(ADP-ribose) synthetase activity which is sensitive to DNA breaks, increased first (24% over control in 1 day, P less than 0.0001), attained the maximum value on the 5th day (952% over control, P less than 0.0001), and started to decline thereafter and approached near the control value on 14th day. Bleomycin treatment induced a rapid change in the level of lung NAD+. After 1 day the level of NAD+ was reduced by 42% compared to the control (P less than 0.001), further declined to 65% (P less than 0.001) on the 3rd day, and stayed at that level until the 7th day. On the 14th day, however, the NAD+ level was still lower (29%, P less than 0.05) but approaching the value in the control animals. The activity of prolyl hydroxylase showed significant increase on the 3rd day (50% over control, P less than 0.0001) after bleomycin administration. The enzyme activity continued to increase until the end of the experiment (490% of control, P less than 0.0001, on Day 14). The content of undialyzable hydroxyproline, a marker for collagen, was also increased significantly in the lung tissue on the 3rd day (30% over control, P less than 0.05), continued to increase and reached the highest level on the 14th day (71% over control, P less than 0.001). A significant increase in the activity of SOD (19% over control, P less than 0.001) was seen on the 5th day which continued to increase and attained the highest value on Day 14 (115% over control, P less than 0.0001).(ABSTRACT TRUNCATED AT 400 WORDS)
Exp Mol Pathol 1985 Oct
PMID:Poly(ADP-ribose) synthetase activity during bleomycin-induced lung fibrosis in hamsters. 241 86

The authors developed a competitive enzyme immunoassay for serum immunoreactive prolyl hydroxylase (SIRPH) as a marker of fibrogenesis, and examined the changes in SIRPH concentrations in rats with carrageenan-induced granuloma and adjuvant arthritis. The effects of such anti-inflammatory agents as prednisolone, pranoprofen, indomethacin, and hydrocortisone were also investigated. Prolyl hydroxylase activity in rats with carrageenan-induced granuloma and adjuvant arthritis increased inflammatory granulation tissue, and the concentrations of SIRPH also increased time dependently. The nontreated controls showed a constant low level of SIRPH. After treatment with anti-inflammatory agents or removal of the granuloma, SIRPH levels decreased coincident with the improvement of clinical symptoms. It was assumed that immunoreactive prolyl hydroxylase was released into the blood stream as a result of increased turnover of the enzyme protein owing to fibrotic disorders. SIRPH could be a useful biochemical marker for assessing therapeutic effects through the actual activity of fibrogenesis.
Exp Mol Pathol 1988 Oct
PMID:Increased serum immunoreactive prolyl hydroxylase in rats with carrageenan-induced granuloma and adjuvant arthritis. 284 81

Serum galactosylhydroxylysyl glucosyltransferase (S-Glu-Gal-Hyl-Tase), liver galactosylhydroxylysyl glucosyltransferase (L-Glu-Gal-Hyl-Tase), liver hydroxylysyl galactosyltransferase (L-Gal-Hyl-Tase), and liver prolyl hydroxylase (L-PH) activities were measured in rats during the development of CCl4-induced cirrhosis (0.2 ml of 33% CCl4 in light mineral oil two times weekly for 10 weeks followed by 6 weeks of no treatment). Serum and liver markers of collagen synthesis increased in a time-dependent manner reaching maximum activity at 6 weeks (S-Glu-Gal-Hyl-Tase, two times; L-PH, two times). These enzyme levels returned to normal during the 4-week recovery period. In a separate 4-week experiment, colchicine (10 micrograms/rat/day) was administered with CCl4. Colchicine prevented the increase in S-Glu-Gal-Hyl-Tase, L-Glu-Gal-Hyl-Tase, and L-Gal-Hyl-Tase induced by CCl4 and resulted in a smaller increase in L-PH. These results demonstrate that S-Glu-Gal-Hyl-Tase elevation occurs following CCl4 because of increased liver collagen synthetic activity and the hepatocellular injury produced by CCl4.
Exp Mol Pathol 1987 Apr
PMID:Enzyme markers of collagen synthesis in carbon tetrachloride-induced fibrosis and during colchicine modification of CCl4-induced liver injury. 303 Jul 97

Intratracheal administration of bleomycin causes pulmonary fibrosis in hamsters. Using this model the activities of lung prolyl hydroxylase and superoxide dismutase and the accumulation of neutral salt soluble and insoluble collagens have been determined. One unit of bleomycin was injected intratracheally to hamsters, whereas control animals received an equivalent volume of sterile saline by the same route. Total lung prolyl hydroxylase activity was significantly elevated at all times following bleomycin treatment. The activity was increased as early as 2 days, peaked to a maximum value of 400% of the control at 14 days, followed by a sharp decline to 235% and 180% of the control activity at 21 and 28 days after bleomycin treatment, respectively. Except for the earliest time (2 days), lung prolyl hydroxylase specific activity was also significantly elevated at all times after bleomycin treatment. A significant increase in both total and specific activities of lung superoxide dismutase was also observed at all times after bleomycin treatment. Total activity peaked to a maximum value of 315% of the control activity at 14 days and the specific activity to a maximum value of 190% of the control at 21 days after bleomycin treatment. Thereafter, both activities declined, but were still significantly elevated over the control at 28 days after the treatment. Lung proline pool size was significantly increased at all times and attained a maximum value of 372% of the control at 14 days after bleomycin treatment. Increases in the lung prolyl hydroxylase and superoxide dismutase activities and in the proline pool size preceded the significant increases in neutral salt soluble and insoluble collagens which occurred at 7 days after bleomycin treatment and continued to be significantly elevated for the remaining period of the study.
Exp Mol Pathol 1983 Dec
PMID:Increases in lung prolyl hydroxylase and superoxide dismutase activities during bleomycin-induced lung fibrosis in hamsters. 619 28

Infection of hamsters by the human liver fluke Opisthorchis viverrini elevated liver procollagen prolyl hydroxylase activity, reflecting increased collagen biosynthesis. The increase was proportional to the intensity of infection. However, the infected liver procollagen prolyl hydroxylase activity decreased after administration of praziquantel 300 mg kg-1 body weight, and approached normal levels two weeks after treatment. In the infected hamsters, praziquantel, at a curative dose, caused a transient increase in serum aminotransferase levels and a small but persistent rise in serum alkaline phosphatase. The drug, however, did not cause changes in these enzyme activities in the uninfected hamsters.
Mol Biochem Parasitol 1983 Dec
PMID:Liver procollagen prolyl hydroxylase in Opisthorchis viverrini infected hamsters after praziquantel administration. 631 7

While it is well known that cellular prolyl hydroxylase activity is increased in the presence of ascorbic acid, the mechanism of this modulation is not fully understood. Ascorbic acid is known to generate reactive oxygen radicals which are involved in the regulation of gene expression through mechanisms involving the synthesis of polyADP-ribose in the nucleus. We examined a possible role for this mechanism in modulating prolyl hydroxylase activity in cultures of human fetal (20 week) and neonatal (foreskin) dermal fibroblasts and IMR-90 fibroblasts. The activity of prolyl hydroxylase in these cells increased in the presence of ascorbate. Ascorbate markedly increased the levels of polyADP-ribose synthetase. The increase in prolyl hydroxylase activity was abolished or decreased by inhibitors of polyADP-ribose synthesis. Our studies suggest that ascorbate may regulate the cellular activity of prolyl hydroxylase by activating epigenetic control mechanisms involving polyADP-ribose.
Cell Mol Biol Res 1993
PMID:Regulation of prolyl hydroxylase by ascorbic acid is mediated by polyADP-ribose synthesis. 817 95

To determine the regulatory role of prolyl hydroxylation in intracellular cardiac procollagen turnover, we examined the effects of prolyl 4-hydroxylase inhibitors (alpha, alpha-dipyridil, 3,4-dihydroxybenzoic acid ethyl ester, pyridine 2,4-dicarboxylic acid ethyl ester) and ascorbic acid on procollagen metabolism by cultured, neonatal rat cardiac fibroblasts. Ascorbate-deficient fibroblasts showed decreased rates of prolyl hydroxylation and total collagen accumulation without a significant reduction in alpha 1(I) and alpha 1(III) mRNA levels. The fraction of newly synthesized procollagens degraded intracellularly was also substantially increased in ascorbate-deficient cells (50 +/- 7 v 30 +/- 3% in ascorbate-deficient v control fibroblasts; P < 0.05). These findings were associated with increased intracellular accumulation of Type I procollagen, enhanced secretion of "underhydroxylated" pro alpha 1 (I) polypeptide into the cell culture medium, and decreased extracellular Type I collagen deposition. Similar results were obtained by treating cells with alpha, alpha-dipyridil (300 microns), and 3,4-dihydroxybenzoic acid ethyl ester (400 microM) in the presence of ascorbate. A major portion of the enhanced degradation of newly synthesized procollagens occurred within acidic intracellular compartments as indicated by the inhibition of procollagen degradation by chloroquine (25 microM). Inhibition of procollagen secretion by colchicine (0.5 micrograms/ml) enhanced the diversion to, and subsequent intracellular degradation of underhydroxylated procollagens in cardiac fibroblast lysosomes. We conclude that inactivation of prolyl 4-hydroxylase increases intracellular accumulation and intralysosomal degradation of newly synthesized cardiac procollagen polypeptides. These observations suggest that procollagen prolyl hydroxylation may be important in the regulation of collagen accumulation by cardiac interstitial cells during fibrotic processes in vivo
J Mol Cell Cardiol 1995 Aug
PMID:Prolyl hydroxylation regulates intracellular procollagen degradation in cultured rat cardiac fibroblasts. 852 10

A differential screen of a tomato root hair cDNA library resulted in the cloning of two cDNAs, Dif10 and Dif54, whose corresponding genes are preferentially expressed in root hair cells as determined by analysis of mRNA levels in various tomato organs. Transcript levels showed no increase in leaves subjected to hormonal and environmental stress treatments. Sequence analysis of the cDNAs revealed high similarity to members of the extension family. Extensions are hydroxyproline-rich glycoproteins (HRGPs) located in the cell wall. In order to study the functional significance of HRGPs in root hairs, tomato seedling roots were treated with micromolar concentrations of 3,4-dehydro-L-proline (Dhp), a selective inhibitor of prolyl hydroxylase. Dhp treatment resulted in changes in root growth and the development of root hairs with reduced hair length, suggesting an important role of HRGPs in hair morphogenesis.
Plant Mol Biol 1997 Nov
PMID:Two genes encoding extension-like proteins are predominantly expressed in tomato root hair cells. 934 72

Fetal placental vessels develop and adapt in order to supply the fetus with nutrients. Immunostaining by antibodies against blood clotting factors, cell-cell and cell-matrix adhesion molecules, intermediate and contractile filaments, matrix components and enzymes give an overall view useful in assessing cell differentiation in placental villi. Endothelial cells stained positively for thrombomodulin, von Willebrand factor, CD34, CD31, cadherin-5, phalloidin and alpha 3-integrin. Trophoblastic cells were positive for cytokeratin, alpha 5 and alpha V integrins, L-prolyl hydroxylase and phalloidin. Myocytes from the media of stem villi exhibited positive vimentin, desmin, alpha-sm-actin and sm-myosin reactions but were CD26 negative. Myofibroblasts were vimentin, desmin, CD26, alpha-sm-actin and sm-myosin positive. Perivascular cells of intermediate and terminal villi were alpha-sm-actin, sm-myosin and anti-high molecular weight melanoma associated antigen (HMWMAA) positive. Trophoblastic and endothelial basement membranes were collagen IV positive. The most specific endothelial markers were cadherin-5, observed only at paracellular clefts, and von Willebrand factor. For perivascular cells, alpha-sm-actin, sm-myosin and HMWMAA provided a specific labeling. Differences in labeling intensity were noted along the cross section of the villous tree (vimentin, desmin, actin, myosin inward gradient). A continuity in the contractile function along the vessel length was indicated by alpha-sm-actin and sm-myosin positive cells, contrasting with the decreased von Willebrand reaction intensity. These data are discussed in relation to cell function and compared to cell culture results.
Cell Mol Biol (Noisy-le-grand) 1999 Feb
PMID:Immunostaining of vascular, perivascular cells and stromal components in human placental villi. 1009 44


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