Hypoxia-Inducible Factor -1 contributes to transcriptional regulation of Bcl2-adenovirus E1B 19KDa -interacting protein in hypoxic cortical neurons
| dc.contributor.author | Atoui, Samira | |
| dc.contributor.examiningcommittee | Hatch, Grant (Pharmacology and Therapeutics) Kong, Jiming (Human Anatomy and Cell Science) | en_US |
| dc.contributor.supervisor | Anderson, Chris (Pharmacology and Therapeutics) | en_US |
| dc.date.accessioned | 2016-04-07T15:38:40Z | |
| dc.date.available | 2016-04-07T15:38:40Z | |
| dc.date.issued | 2016 | |
| dc.degree.discipline | Pharmacology and Therapeutics | en_US |
| dc.degree.level | Master of Science (M.Sc.) | en_US |
| dc.description.abstract | PARP-1 has been identified as a major player in apoptotic pathways. Its excessive activation causes mitochondrial dysfunction, permeability, and AIF mitochondrion-to-nucleus translocation. It has been suggested that PARP-1 interacts indirectly with Bnip3, a mitochondrial pro-apoptotic factor. However, the mechanistic linkage is still not well understood. Our lab has shown that cytosolic/nuclear NAD+ depletion is a hallmark for PARP-1 over activation and inhibition of sirtuin activity. Specifically in my project, we think that PARP-1 induced- NAD+ depletion and sirtuin inhibition causes hyperacetylation of the α subunit of the transcription factor HIF-1 allowing increased HIF-1 binding to Bnip3 upstream promoter, and increased Bnip3 expression. Indeed, our PARP-1 Knock out neurons, MNNG and PJ34 treatment, chromatin immunoprecipitation, and HIF-1α loss of function studies strongly confirmed the necessity of HIF-1 to increase Bnip3 expression in hypoxia. Overall, our research suggests a role for HIF-1 in increasing PARP-1 dependent Bnip3 expression in hypoxic models. | en_US |
| dc.description.note | May 2016 | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/31183 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.subject | Stroke | en_US |
| dc.subject | Hypoxia | en_US |
| dc.subject | PARP-1 | en_US |
| dc.subject | Bnip3 | en_US |
| dc.subject | HIF-1 | en_US |
| dc.subject | mitochondrial | en_US |
| dc.title | Hypoxia-Inducible Factor -1 contributes to transcriptional regulation of Bcl2-adenovirus E1B 19KDa -interacting protein in hypoxic cortical neurons | en_US |
| dc.type | master thesis | en_US |