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)

Since the demonstration, in 1972, of the essentiality of silicon in higher animals, bio-inorganic chemists have speculated about the site and mechanism of action of silicon. Bone and connective tissue have been identified as tissues that are altered in the absence of silicon. Si-C bonds are foreign to biochemistry so organic bonding must be via Si-O-C, but the instability of the ester bond in aqueous solution at pH 7.4 has prompted us to investigate the interactions of silicic acid. Silicic acid could, by hydrogen bonding, alter the conformation of organic macromolecules, since hydrogen bond association can inhibit silanol condensation. However, silanols are also able to interact with metal ions that are basic at physiological pH, e.g. Fe3+ or Al3+ but not Ca2+, and such interactions are known in geochemistry. The observed effects of Si on hard and soft tissue could therefore result from interactions of Si(OH)4 with Fe3+, which is involved in connective tissue synthesis (via enzymes, e.g. prolyl hydroxylase) and damage (via iron-catalysed radical generation), or with Al3+ which exerts toxic effects at sites (bone and brain) at which Si has also been observed. Although we have demonstrated several Fe3+/Si interactions, we have not been able to show their relevance in a biochemical context. Al3+ interacts with Si(OH)4 in aqueous solution and preliminary experiments have suggested that silicic acid can counteract deleterious effects of aluminium, for example the activity of prolyl hydroxylase, an observation with implications not only in osteogenesis but also in Alzheimer's disease and aluminium toxicity in acidified waters.
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PMID:Biological implications of the interaction (via silanol groups) of silicon with metal ions. 374 28

The effect of silica on collagen biosynthesis by confluent monolayers of WI-38 fibroblast cultures was examined by a more comprehensive method of analysis. The presence of the particulates had no direct effect on protein (collagen) synthesis, proline incorporation or prolyl hydroxylase activity; the latter is determined by the degree of hydroxylation. Silica, however, was highly toxic to the cells.
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PMID:Tripeptide analysis of collagen synthesized by silica-exposed fibroblast cultures. 630 31

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