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)

Endothelial cells (EC) exposed to hypoxia upregulate a unique set of five stress proteins. These proteins are upregulated in human and bovine aortic and pulmonary artery EC and are distinct from heat shock or glucose-regulated proteins. We previously identified two of these proteins as the glycolytic enzymes glyceraldehyde-3-phosphate dehydrogenase and enolase and postulated that the remaining proteins were also glycolytic enzymes. Using SDS-PAGE, tryptic digestion, and NH(2)-terminal amino acid sequencing, we report here the identification of the 56-kDa protein as protein disulfide isomerase (PDI). PDI is upregulated by hypoxia at the mRNA level and follows a time course similar to that of the protein, with maximal upregulation detected after exposure to 18 h of 0% O(2). Neither smooth muscle cells nor fibroblasts upregulate PDI to the same extent as EC, which correlates with their decreased hypoxia tolerance. Upregulation of PDI specifically in EC may contribute to their ability to tolerate hypoxia and may occur through PDI's functions as a prolyl hydroxylase subunit, protein folding catalyst, or molecular chaperone.
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PMID:Identification of protein disulfide isomerase as an endothelial hypoxic stress protein. 1194 64

Hypoxia-inducible factor (HIF) prolyl 4-hydroxylases are a family of iron- and 2-oxoglutarate-dependent dioxygenases that negatively regulate the stability of several proteins that have established roles in adaptation to hypoxic or oxidative stress. These proteins include the transcriptional activators HIF-1alpha and HIF-2alpha. The ability of the inhibitors of HIF prolyl 4-hydroxylases to stabilize proteins involved in adaptation in neurons and to prevent neuronal injury remains unclear. We reported that structurally diverse low molecular weight or peptide inhibitors of the HIF prolyl 4-hydroxylases stabilize HIF-1alpha and up-regulate HIF-dependent target genes (e.g. enolase, p21(waf1/cip1), vascular endothelial growth factor, or erythropoietin) in embryonic cortical neurons in vitro or in adult rat brains in vivo. We also showed that structurally diverse HIF prolyl 4-hydroxylase inhibitors prevent oxidative death in vitro and ischemic injury in vivo. Taken together these findings identified low molecular weight and peptide HIF prolyl 4-hydroxylase inhibitors as novel neurological therapeutics for stroke as well as other diseases associated with oxidative stress.
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PMID:Hypoxia-inducible factor prolyl 4-hydroxylase inhibition. A target for neuroprotection in the central nervous system. 1622 10

Oxidative stress has been implicated in the pathogenesis of neuronal degenerative diseases. It is also widely known that oxidative stress induces mitogen-activated protein kinase (MAPK) signaling cascades. In this study, we used proteomic analysis to investigate the role of the MAPK pathway in oxidative stress-induced neuronal cell death. The results demonstrated that several proteins, including eukaryotic translation elongation factor 2 (eEF2) and enolase I, showed a differential expression pattern during the neuronal cell death process, and this was MAPK pathway dependent. Several chaperone and cytoskeletal proteins including heat shock protein 70, calreticulin, vimentin, prolyl 4-hydroxylase beta polypeptide, and transgelin 2 were up-or down-regulated, despite their expressions not depending on the MAPK pathway. These findings strongly suggest that the expressions of proteins which play protective roles are independent of the MAPK pathway. On the other hand, eEF2 and enolase I may be the downstream targets of the MAPK pathway.
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PMID:A proteomic analysis of the effect of MAPK pathway activation on L-glutamate-induced neuronal cell death. 1712 46

Previous studies have shown that microgroove-initiated contact guidance can induce bone formation in osteoprogenitor cells (OPGs) and produce changes in the cell proteome. For proteomic analysis, differential in-gel electrophoresis (DIGE) can be used as a powerful diagnostic method to provide comparable data between the proteomic profiles of cells cultured in different conditions. This study focuses on the response of OPGs to a novel nanoscale pit topography with osteoinductive properties compared with planar controls. Disordered near-square nanopits with 120 nm diameter and 100 nm depth with an average 300 nm centre-to-centre spacing (300 nm spaced pits in square pattern, but with +/-50 nm disorder) were fabricated on 1x1 cm2 polycaprolactone sheets. Human OPGs were seeded onto the test materials. DIGE analysis revealed changes in the expression of a number of distinct proteins, including upregulation of actin isoforms, beta-galectin1, vimentin and procollagen-proline, 2-oxoglutarate 4-dioxygenase and prolyl 4-hydroxylase. Downregulation of enolase, caldesmon, zyxin, GRASP55, Hsp70 (BiP/GRP78), RNH1, cathepsin D and Hsp27 was also observed. The differences in cell morphology and mineralization are also reported using histochemical techniques.
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PMID:Proteomic analysis of human osteoprogenitor response to disordered nanotopography. 1906 73