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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Patton, Stephanie M. Volitakis, Irene Cherny, Robert A. Seeley, Todd Lamanna, Joseph C. Bush, Ashley I. Shah, Sapan Langsetmo, Ingrid Aminova, Leila Ratan, Rajiv R. Connor, James R. Gunzler, Volkmar Siddiq, Ambreena Ayoub, Issam A. Chavez, Juan C. |
| Description | Author Affiliation: Siddiq A ( Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA.) |
| Abstract | 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. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 50 |
| Volume Number | 280 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2005-12-16 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Basic Helix-Loop-Helix Transcription Factors Metabolism Hypoxia-Inducible Factor 1, Alpha Subunit Animals Chemistry Brain Central Nervous System Cerebral Cortex Embryology Cyclin-Dependent Kinase Inhibitor P21 Erythropoietin Fluoresceins Luciferases Mass Spectrometry Microscopy, Fluorescence Models, Molecular Molecular Weight Neurons Oxidative Stress Peptides Phosphopyruvate Hydratase Procollagen-Proline Dioxygenase Protein Binding Rats, Sprague-Dawley Up-Regulation Vascular Endothelial Growth Factor A Zinc Research Support, N.I.H., Extramural Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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