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. / May 2016
| Identifer | oai:union.ndltd.org:MANITOBA/oai:mspace.lib.umanitoba.ca:1993/31183 |
| Date | 07 April 2016 |
| Creators | Atoui, Samira |
| Contributors | Anderson, Chris (Pharmacology and Therapeutics), Hatch, Grant (Pharmacology and Therapeutics) Kong, Jiming (Human Anatomy and Cell Science) |
| Source Sets | University of Manitoba Canada |
| Detected Language | English |
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