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)

A staging scheme for hepatocellular carcinoma was presented at an International Symposium on Liver Cancer in Kampala, Uganda in 1971. Historical, clinical, and laboratory aspects of that staging scheme were examined for prognostic significance in 72 untreated patients with this disease studied at the Uganda Cancer Institute. The median survival for the entire group was 1 month. The presence of a serum bilirubin concentration of greater than 2 mg/100 ml or weight loss greater than 25 percent of body weight were the poorest prognostic features. Other factors with prognostic significance were visible abdominal collateral circulation, ascites, tumor differentiation, and serum levels of alkaline phosphatase, SGOT, alpha fetoprotein, and proline hydroxylase. A modified staging scheme is presented which defines three prognostically different groups of Ugandan patients. It is hoped this staging scheme will serve as a stimulus for analysis of similar prognostic features in other populations of patients with hepatocellular carcinoma.
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PMID:A staging system for hepatocellular carcinoma: prognostic factors in Ugandan patients. 4 61

Two metabolically distinct types of bone cell populations were isolated from mouse calvaria by a repetitive digestive procedure with a mixture of collagenase and trypsin. Cells released early in the digestion showed approximately two-fold increases in cAMP when treated with either parathormone or calcitonin. These populations were denoted CT type. Later eluting cells showed larger parathormone-induced increases in cAMP but did not respond to calcitonin. These populations were denoted PT type. Six metabolic and enzymatic activites were measured in the two types of populations: acid and alkaline phosphatases, hyaluronate synthesis, citrate decarboxylation, prolyl hydroxylase, and general protein synthesis. Although each of these activites was present in both cell types, the basal levels of acid phosphatase and hyaluronate synthesis were higher in the CT cells, whereas alkaline phosphatase, citrate decarboxylation, and prolyl hydroxylase were higher in te PT cells. Parathormone stimulated acid phosphatase and hyaluronate synthesis by 100-200% only in the CT cells; in inhibited alkaline phosphatase, citrate decarboxylation, and prolyl hydroxylase by 75-90% only in the PT cells. Calcitonin alone had no effect on any of these activities other than cAMP production, but in inhibited the action of parathormone in the CT cells. The sensitivities, time courses of development,and magnitudes of these hormonal effects were similar to those observed previously in intact calvaria, indicating that the isolated cell system is a reliable model for the study of bone metabolism. Based on the metabolic responses of the cells, we postulate that the CT type of populations is enriched in osteoclasts and, possibly, osteocytes, and the PT type of population is enriched in osteoblasts.
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PMID:Biochemical characterization with parathormone and calcitonin of isolated bone cells: provisional identification of osteoclasts and osteoblasts. 18 58

The effects of smokeless tobacco extract (STE) and prolyl hydroxylase inhibitors on protein synthesis by isolated osteoblast-like cells were compared. STE and 2,2'dipyridyl markedly inhibited alkaline phosphatase (Alpase) and [3H]proline hydroxylation without affecting glycolysis (lactate production). However, pyridine 2,5-dicarboxylate (2,5-PDC) did not inhibit [3H] proline hydroxylation, Alpase activity, or glycolysis at moderate concentrations. The [3H]hydroxyproline to [3H]proline ratio in the cell layers demonstrated a concentration-dependent decrease with increasing STE and inhibitor concentrations. In the cell layers, the collagenous protein (CP) content was decreased after exposure to STE, 2,2'dipyridyl, and 2,5-PDC and the noncollagenous protein (NCP) content was decreased after exposure to STE and 2,5-PDC. However, the effects on CP were at least twofold greater than on NCP. Similar results were observed regarding protein released to the culture medium. These data demonstrate that STE, like 2,2'dipyridyl, inhibits the hydroxylation of proline and the synthesis of collagenase-digestible protein.
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PMID:Comparison of the effects of smokeless tobacco extract with the effects of prolyl hydroxylase inhibitors on collagenous and noncollagenous protein synthesis by osteoblasts. 166 21

Prolyl hydroxylase was purified from human placentae, specific antiserum against it was prepared, and a new radioimmunoassay system employing 125I-labelled enzyme preparation was established. The molecular weight of the placental enzyme was shown to be 320,000 by gel filtration. SDS-polyacrylamide gel electrophoresis showed two bands of unequal intensity having molecular weights of 60,000 and 130,000. Their amino acid compositions were identical to each other, suggesting the polypeptide with a molecular weight of 130,000 might be a dimer of the polypeptide with a molecular weight of 60,000. The new radioimmunoassay established had a sensitivity of the order of 10 ng/ml, indicating it was more sensitive than previous radioimmunoassay employing 3H-labelling method. Clinical studies on patients with liver diseases disclosed that the concentrations of serum immunoreactive prolyl hydroxylase were elevated both in cases of hepatocellular damage and in cases of cholestasis. In cases of hepatocellular damage the enzyme behaved like cytoplasmic enzymes such as glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and lactic dehydrogenase, but in cases of cholestasis it resembled biliary enzymes such as alkaline phosphatase and gamma-glutamyl transpeptidase. This result might be associated with the peculiar location of the enzyme within the cell, in the membrane of rough endoplasmic reticulum.
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PMID:Human prolyl hydroxylase. Purification, radioimmunoassay and clinical studies in liver diseases. 299 Oct 66

An experimental animal model designed specifically to simulate liver fibrosis and cirrhosis in childhood is described. Phenobarbitone was administered continuously from the 4th day of life and carbon tetrachloride intermittently from the 13th day to developing rats for 10 weeks. Treated animals showed hepatic necrosis, hepatic regeneration and a progressive increase in hepatic fibrosis; cirrhosis developed before the animals reached sexual maturity at 72 days or were fully grown. Hepatic prolyl hydroxylase activity increased to a maximum level after 20 days of treatment, before increased hepatic collagen could be detected, and fell to a lower level as cirrhosis became established. Serum activities of alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase gave a similar pattern, a marked increase at 20 days of age followed by a fall to near normal levels as hepatic damage became more severe. By the 26th day of life hepatic collagen levels were increased significantly and rose thereafter progressively as fibrosis became more widespread throughout the liver. Cirrhosis developed between the 38th and 75th days. Cirrhosis remained 10 weeks after discontinuation of treatment with phenobarbitone and carbon tetrachloride treatment.
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PMID:Carbon tetrachloride-induced hepatic fibrosis and cirrhosis in the developing rat: an experimental model of cirrhosis in childhood. 630 21

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.
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PMID:Liver procollagen prolyl hydroxylase in Opisthorchis viverrini infected hamsters after praziquantel administration. 631 7

Ascorbic acid is necessary for expression of the osteoblast phenotype. We examined whether Na(+)-dependent transport is required for MC3T3-E1 preosteoblast cells to respond to vitamin C and investigated the role of membrane transport in the intracellular accumulation and function of ascorbate. MC3T3-E1 cells were found to possess a saturable, stereoselective, Na(+)-dependent ascorbic acid transport activity that is sensitive to the transport inhibitors sulfinpyrazone, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, and phloretin. Transport activity showed no competition with glucose or 2-deoxyglucose and was not inhibited by cytochalasin B, indicating that it is distinct from known hexose transporters. On addition of 100 microM ascorbic acid to the extracellular medium, intracellular concentrations of 10 mM were reached within 5-10 h and remained constant for up to 24 h. A good correlation was observed between intracellular ascorbic acid concentration and rate of hydroxyproline synthesis. Although ascorbic acid was transported preferentially compared with D-isoascorbic acid, both isomers had equivalent activity in stimulating hydroxyproline formation once they entered cells. Marked stereoselectivity for extracellular L-ascorbic acid relative to D-isoascorbic acid was also seen when alkaline phosphatase and total hydroxyproline were measured after 6 days in culture. Moreover, ascorbic acid transport inhibitors that prevented intracellular accumulation of vitamin blocked the synthesis of hydroxyproline. Thus Na(+)-dependent ascorbic acid transport is required for MC3T3-E1 cells to achieve the millimolar intracellular vitamin C concentrations necessary for maximal prolyl hydroxylase activity and expression of the osteoblast phenotype.
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PMID:Requirement for Na(+)-dependent ascorbic acid transport in osteoblast function. 761 63

Nutritional and pharmacological factors are needed to prevent bone loss that occurs with increasing age. The chemical compounds that act on bone metabolism as nutrients in food, however, are poorly understood. The effect of resveratrol, a natural phytoestrogen, on the proliferation and differentiation of osteoblastic MC3T3-E1 cells was studied. Resveratrol dose-dependently increased DNA synthesis (10(-9)-10(-7) M) of MC3T3-E1 cells. In addition, resveratrol increased alkaline phosphatase (ALP) activity and prolyl hydroxylase activity of MC3T3-E1 cells (10(-6)-10(-5) M). Moreover, the antiestrogen tamoxifen eliminated the stimulation of MC3T3-E1 cells on the proliferation and ALP activity by resveratrol. On the other hand, resveratrol inhibited prostaglandin E2 production in MC3T3-E1 cells (10(-8)-10(-6) M). Our present study is the first to demonstrate that resveratrol directly stimulates cell proliferation and differentiation of osteoblasts.
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PMID:Resveratrol stimulates the proliferation and differentiation of osteoblastic MC3T3-E1 cells. 991 20

It was hypothesized that the widespread structural defect of collagen in connective tissue of vitamin B6 deficient-animals and the consequent alteration in bone biomechanical properties cause an additional stress to their inflamed swollen tibiotarsometatarsal joints. The present study showed a 32% elevation (P < 0.02) in mean plasma free cortisol concentration. Vitamin D metabolism was impaired but without changing plasma calcium homeostasis and bone mineral content. Mean plasma calcitriol [1,25(OH)2D] concentration was significantly reduced (P < 0.001). Because plasma calcidiol concentration did not change, we speculated that either renal 25-hydroxycalciferol-1alpha-hydroxylase activity was reduced or 1,25(OH)2D turnover was increased. Plasma osteocalcin, an index of osteoblast function related to bone formation, was significantly decreased (P < 0.05). This adverse effect on osteoblasts was consistent with the reduction of bone specific alkaline phosphatase activity (another index of bone formation) found in a previous study. The excess of cortisol may have impaired these bone cells functions directly and (or) indirectly via the decline in calcitriol synthesis. Plasma hydroxyproline concentrations in B6-deficient animals were found to be significantly reduced (P < 0.001), suggesting that cortisol in excess had also a suppressive effect on another hydroxylase, namely tissue (mainly bone and liver) prolyl hydroxylase. The bone uncoupling (in formation and resorption) associated with vitamin B6 deficiency seems to be due to secondary hypercortisolism and (or) another unknown factors but not related to a change in bone modulators such as IGF-1 and eicosanoids.
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PMID:Perturbations in factors that modulate osteoblast functions in vitamin B6 deficiency. 1110 Sep 39

Silicon deficiency in animals leads to bone defects. This element may therefore play an important role in bone metabolism. Silicon is absorbed from the diet as orthosilicic acid and concentrations in plasma are 5-20 microM. The in vitro effects of orthosilicic acid (0-50 microM) on collagen type 1 synthesis was investigated using the human osteosarcoma cell line (MG-63), primary osteoblast-like cells derived from human bone marrow stromal cells, and an immortalized human early osteoblastic cell line (HCC1). Collagen type 1 mRNA expression and prolyl hydroxylase activity were also determined in the MG-63 cells. Alkaline phosphatase and osteocalcin (osteoblastic differentiation) were assessed both at the protein and the mRNA level in MG-63 cells treated with orthosilicic acid. Collagen type 1 synthesis increased in all treated cells at orthosilicic acid concentrations of 10 and 20 microM, although the effects were more marked in the clonal cell lines (MG-63, HCCl 1.75- and 1.8-fold, respectively, P < 0.001, compared to 1.45-fold in the primary cell lines). Treatment at 50 microM resulted in a smaller increase in collagen type 1 synthesis (MG-63 1.45-fold, P = 0.004). The effect of orthosilicic acid was abolished in the presence of prolyl hydroxylase inhibitors. No change in collagen type 1 mRNA level was seen in treated MG-63 cells. Alkaline phosphatase activity and osteocalcin were significantly increased (1.5, 1.2-fold at concentrations of 10 and 20 microM, respectively, P < 0.05). Gene expression of alkaline phosphatase and osteocalcin also increased significantly following treatment. In conclusion, orthosilicic acid at physiological concentrations stimulates collagen type 1 synthesis in human osteoblast-like cells and enhances osteoblastic differentiation.
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PMID:Orthosilicic acid stimulates collagen type 1 synthesis and osteoblastic differentiation in human osteoblast-like cells in vitro. 1263 84


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