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)

To study the role of (pro)collagen synthesis in the differentiation of rat L6 skeletal myoblasts, a specific inhibitor of collagen synthesis, ethyl-3,4-dihydroxybenzoate (DHB), was utilized. It is shown that DHB reversibly inhibits both morphological and biochemical differentiation of myoblasts, if it is added to the culture medium before the cell alignment stage. The inhibition is alleviated partially by ascorbate, which along with alpha-ketoglutarate serves as cofactor for the enzyme, prolyl hydroxylase. DHB drastically decreases the secretion of procollagen despite an increase in the levels of the mRNA for pro alpha 1(I) and pro alpha 2(I) chains. Probably, the procollagen chains produced in the presence of DHB, being underhydroxylated, are unable to fold into triple helices and are consequently degraded in situ. Along with the inhibition of procollagen synthesis, DHB also decreases markedly the production of a collagen-binding glycoprotein (gp46) present in the ER. The results suggest that procollagen production and/or processing is needed as an early event in the differentiation pathway of myoblasts.
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PMID:Ethyl-3,4-dihydroxybenzoate inhibits myoblast differentiation: evidence for an essential role of collagen. 215 80

Protein disulphide isomerase (PDI) has been shown to be a multifunctional protein capable of catalysing disulphide-bond formation and isomerization, and of participating as a non-catalytic subunit of prolyl 4-hydroxylase (P4-H) and microsomal triacylglycerol transfer protein. It has also been proposed to function as a molecular chaperone during the refolding of denatured proteins in vitro. To investigate its potential role as a molecular chaperone within a cellular context, we studied the folding, modification and assembly of type X collagen in semi-permeabilized cells. Using this approach, we demonstrate that depletion of ATP has no effect on the rate or extent of helix formation, indicating that the individual triple helical regions do not interact with the molecular chaperone immunoglobulin heavy-chain binding protein (BiP). However, PDI was shown to interact transiently with type X during helix formation in a role related to its function as the beta subunit of P4-H. Once the collagen triple helix was formed, PDI re-associated, indicating a role in preventing the premature assembly of this molecule into higher-order structures. This interaction was not thiol dependent, as a type X polypeptide that did not contain any cysteine residues was able to fold correctly and interact with PDI. Both PDI and the collagen-binding protein hsp47 showed a similar pH-dependent interaction with folded collagen, dissociating when the pH was lowered to pH 6.0. These results suggest a role for PDI in chaperoning type X collagen during its transport through the cell.
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PMID:Thiol-independent interaction of protein disulphide isomerase with type X collagen during intra-cellular folding and assembly. 956 Mar 6