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)

The aim of the study was to observe pulpal collagen synthesis in response to trauma and to glucocorticoid medication. The material consisted of 290 rabbit pulps and 76 human premolar pulps. Collagen synthesis was determined by incubating whole pulps in a medium containing [14C]proline, and measuring the formation of [14C]hydroxyproline. The effect of glucocorticoids was studied in vitro using rabbit pulps. Hydrocortisone and dexamethasone inhibited collagen synthesis, whereas prednisolone had no marked effect. Hydrocortisone was found to inhibit the synthesis of [14C]hydroxyproline in neutral salt soluble and insoluble non-dialyzable collagen fractions. [14C]hydroxyproline in the dialyzable fraction was increased, suggesting that hydrocortisone increased collagen degradation. In the human material, premolar pulps were experimentally exposed and then medicated with capping agents. The contralateral teeth were exposed and capped with other capping materials, in some cases they were left as intact controls. The exposure led to an increase in the collagen synthesis as indicated by increased [14C]hydroxyproline formation and elevated protocollagen proline hydroxylase activity in the pulp. This enzyme activity was suppressed in pulps capped with a glucocorticoid paste. In addition, the collagen synthesis rate was lower in pulps treated with another glucocorticoid containing compound, when compared to pulps capped with a calcium hydroxide preparation.
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PMID:Effects of topical glucocorticoid medication on collagen biosynthesis in the dental pulp. 18 44

During the different stages of granuloma formation peptidyl prolyl hydroxylase activity and neutral salt soluble collagen were determined in the granuloma tissue. In parallel peptidyl prolyl hydroxylase activity, "collagen-like protein", and free hydroxyproline were measured in the serum of the same animals at correspondant time distances. A close correlation was found between the enzyme activity and the other parameters of collagen synthesis. These results confirm the conclusion that hydroxylation of polypeptide may be a rate limiting step in collagen biosynthesis. In addition the investigations revealed a close correlation between enzyme activity in the tissue and enzyme activity in the serum.
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PMID:[Peptidyl prolyl hydroxylase activity in relation to the actual collagen biosynthesis in cotton pellet granuloma of guinea pig (author's transl)]. 19 77

The activity of procollagen prolyl hydroxylase was measured in fibrotic liver obtained from mice with hepatosplenic schistosomiasis, an animal model of the most prevalent form of human liver fibrosis. Measurable activity of prolyl hydroxylase in fibrotic liver supernatants was 47-fold higher than that of normal liver. The effect of prolyl hydroxylase inhibition on collagen synthesis in fibrotic liver slices was studied, using 8,9-dihydroxy-7-methyl benzo[b]quinolizinium bromide (GPA 1734). This compound was shown in other systems to inhibit prolyl and lysyl hydroxylations by iron chelation at concentrations which did not affect total protein synthesis. The formation of nondialyzable labelled hydroxyproline was inhibited by GPA 1734, 40, 70 and 95% at 30, 50 and 100 micrometer, respectively. Incorporation of proline into total liver protein was unaffected at 30 and 50 micrometer, but was inhibited 20% at 100 micrometer GPA 1734. Underhydroxylated collagen synthesized by liver slices with GPA 1734 was extracted with neutral salt solution and was subsequently hydroxylated with partially-purified prolyl hydroxylase to the same extent as control material synthesized in the absence of GPA 1734.
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PMID:Liver collagen hydroxylation in murine schistosomiasis. 20 35

Rats of Wistar strain, of same age, were kept on iron free diet up to nearly absolute iron deficiency in iron depots. Afterwards granuloma was produced by implantation of cotton pellets subcutaneously. For characterization of the collagen biosynthesis in the granuloma the neutral salt soluble collagen and the activity of the prolyl hydroxylase were measured in the granuloma 4, 8 and 12 days after cotton pellet implantation. At the same time "collagen-like" protein was determined in the serum of the animals. The enzyme activity was statistically significant lower in the granuloma of animals on iron deficiency than in the granuloma of the comparable groups on normal diet. Statistically significant higher concentration of neutral salt soluble collagen was found 8 and 12 days after cotton pellet implantation in the group on iron free diet. There was no significant difference as to the serum levels of "collagen-like" protein in serum.
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PMID:[Parameters of collagen biosynthesis in cotton pellet granuloma of rats on iron deficiency (author's transl)]. 21 Apr 87

The effect of guanethidine on collagen biosynthesis in the aorta and mesenteric artery was investigated in desoxycorticosterone acetate (DOCA)-salt hypertensive rats. Prolyl hydroxylase activity (EC 1.14.11.2; proline, 2-oxoglutarate dioxygenase) and 14C-proline incorporation into collagen, two markers of collagen biosynthesis, were significantly increased in blood vessels of hypertensive rats compared with those of controls. When guanethidine (5 mg/kg, i.p.) was given daily to the hypertensive rats for 4 weeks, the blood pressure was decreased to 150 +/- 7 mm Hg, whereas the blood pressure of the untreated hypertensive rats was 218 +/- 10 mm Hg. Prolyl hydroxylase activity in the aorta and mesenteric artery and 14C-proline incorporation into aortic collagen were significantly reduced concomitant with the decrease in blood pressure. These results suggest that the decrease in vascular collagen biosynthesis in hypertensive rats treated with guanethidine is related to the lowering of their blood pressure.
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PMID:Effect of guanethidine on collagen biosynthesis in blood vessels of hypertensive rats. 22 20

Collagen synthesis was increased in aortas, mesenteric arteries, cerebral microvessels, pial artery, basilar artery and decreased in the heart of rats made hypertensive with deoxycorticosterone acetate-salt or the spontaneously hypertensive animal. The markers of collagen biosynthesis that were elevated were prolyl hydroxylase, prolyl hydroxylase-related antigen, total collagen content and the incorporation of labelled proline into total protein and into collagen. The antihypertensive drugs reserpine and chlorthiazide could both prevent the increase or reduce the increase in collagen synthesis.
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PMID:Increased vascular collagen biosynthesis by hypertension and reversal by antihypertensive drugs. 63 Jan 32

The hexapeptide Hyp-Gly-Pro-Lys-Gly-Glu was synthesized as a potential substrate for collagen lysyl hydroxylase. Kinetic data on the interaction of this peptide with purified chicken embryo lysyl hydroxylase showed that the hexapeptide is a moderately good substrate having Km, Vmax, and Kcat/Km values comparable to those of synthetic peptide substrates having longer chain lengths. Circular dichroism spectral data suggested a consecutive beta turn or 3(10) helical conformation for the peptide in trifluoroethanol. The two-dimensional 1H-TOCSY spectrum of the peptide in dimethylsulfoxide permitted complete assignment of all the protons in the hexapeptide. Through-space connectivities between protons in the peptide molecule were obtained from two-dimensional 1H-NOESY spectral data on the peptide. Using the distances calculated from these data as input constraints, the minimum-energy conformation of the peptide was computed. These calculations and an unconstrained Monte Carlo molecular simulation both led to a folded conformation for the hexapeptide with dihedral angles close to a set of consecutive beta turns as the lowest-energy conformer. This structure is stabilized further by a salt bridge between the side chains of Lys4 and Glu6. Several other conformers energetically close to the minimum-energy conformer exhibited the structural features of the latter except for variations at the N-terminal end and in the side chains. In conjunction with data obtained earlier on lysyl hydroxylase (P. Jiang and V. S. Ananthanarayanan, 1991, J. Biol. Chem. 266, 22960-22967) and the functionally related prolyl hydroxylase (P. L. Atreya and V. S. Ananthanarayanan, 1991, J. Biol. Chem. 266, 2852-2858), the present results suggest that the folded beta turn in the respective peptide substrate may be the structural determinant at the catalytic sites of these enzymes. Additional structural features may govern the effective binding of the peptide at the enzymes' active sites.
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PMID:Conformation of a synthetic hexapeptide substrate of collagen lysyl hydroxylase. 152 30

Alterations in extracellular matrix occur in many chronic liver diseases leading to the formation of hepatic fibrosis. We have studied the effects of the putative hepatoselective fibrosuppressive compound HOE 077, a proinhibitor of prolyl 4-hydroxylase, on normal adult human and rat hepatocytes in primary culture. In human hepatocyte cultures, the cytotoxicity of HOE 077 was assessed after a 20-h treatment at concentrations ranging from 0.125 to 2 mg/ml of medium. No significant change was found in cell morphology, neutral red uptake, red oil staining, lactate dehydrogenase release, tetrazolium salt reduction, ethoxyresorufin O-deethylase activity and protein synthesis; however, HOE 077 slightly decreased DNA synthesis at 2 mg/ml. In rat hepatocyte cultures, the cytotoxicity of the compound was assessed by testing the same parameters after a daily exposure of cultures for 2 days or 4 days, at concentrations ranging from 0.25 to 4.5 mg/ml of medium. Whatever the concentration, the compound had no obvious morphological effect. However, hepatocytes were less spread at the concentration of 4.5 mg/ml. HOE 077 at 2 mg/ml slightly decreased neutral red uptake but was without obvious effect on protein synthesis after 2 days. By contrast, on day 4, protein synthesis was markedly reduced in hepatocyte cultures exposed to HOE 077 at 4.5 mg/ml. Hydroxyproline content determination in media from 4-day-old hepatocyte cultures incubated with HOE 077 at 0.5 to 4.5 mg/ml, showed a dose-dependent decrease in the hydroxyproline/proline ratio in acetic acid soluble material. By indirect immunoperoxidase, intracellular collagen IV was found to be inhibited in hepatocyte cultures after 4 days of exposure to 4.5 mg/ml HOE 077.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of the prolyl 4-hydroxylase proinhibitor HOE 077 on human and rat hepatocytes in primary culture. 166 68

Collagen synthesis is increased in the aortas, mesenteric arteries, and to a lesser extent, in the hearts of rats either made hypertensive with desoxycorticosterone acetate-salt or that are spontaneously hypertensive. Several markers of collagen biosynthesis were shown to be increased, including prolyl hydroxylase (EC 1.14.11.2; proline, 2-oxoglutarate dioxygenase), prolyl hydroxylase-related antigen, total collagen content, and the incorporation of [(3)H]proline into total protein and into collagen. The antihypertensive agents chlorothiazide and reserpine, when administered before the onset of hypertension in the rats treated with desoxycorticosterone acetate-salt, prevented or diminished the increase in collagen biosynthesis. When reserpine was given after the onset of hypertension, prolyl hydroxylase activity was decreased concomitant with the decrease in blood pressure. Treatment with reserpine is particularly effective in diminishing arterial prolyl hydroxylase activity.
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PMID:Increased collagen synthesis in blood vessels of hypertensive rats and its reversal by antihypertensive agents. 437 97

Changes in arterial collagen synthesis and the effects of P-1894B, a potent inhibitor of prolyl hydroxylase, were investigated on rat hypertension, induced by deoxycorticosterone acetate (DOCA) and salt. In DOCA-salt hypertensive rats, prolyl hydroxylase activity increased significantly in the abdominal aorta and in the mesenteric artery. Incorporation of 14C-proline into the thoracic aorta, abdominal aorta and mesenteric artery was higher and the hydroxyproline content of the abdominal aorta and mesenteric artery was higher than in the control rats. Treatment with P-1894B significantly inhibited prolyl hydroxylase activity, reduced arterial collagen synthesis, but did not prevent or reverse hypertension.
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PMID:Effects of prolyl hydroxylase inhibition on arterial collagen synthesis and blood pressure in hypertensive rats. 609 59


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