Sirtuins are a family of nicotinamide adenine dinucleotide - dependent enzymes, which have gained recent interest due to their ability to directly or indirectly regulate cell metabolism, oxidative response mechanisms and cellular senescence. A mitochondrial sirtuin SIRT3, although still relatively under-investigated, regulates mitochondrial processes through deacetylation of metabolic enzymes and components of electron transport chain. We hypothesized that SIRT3 is a mitochondrial cytoprotective factor that exerts its function by decreasing reactive oxygen species levels, and protecting cells from oxidative stress. HEK-293 cells over-expressing SIRT3 exhibit reduced mitochondrial membrane potential and reactive oxygen species levels under basal conditions. In addition, cells over-expressing SIRT3 are less sensitive to hydrogen peroxide and glucose deprivation/glucose reperfusion induced-cell death. Since SIRT3 expression in the brain has not yet been investigated, its expression pattern in the rodent brain was characterized. Our results showed that SIRT3 mRNA and protein levels are robustly expressed in different regions of the adult rodent brain and their expression increases with age. Furthermore, SIRT3 is expressed predominantly in astrocytes in cultures derived from rat primary E18 cortical cells. These results suggest that SIRT3 possesses cytoprotective potential, and that its actions in the brain regulate astrocyte physiology.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/31443 |
| Date | 20 December 2011 |
| Creators | Sidorova, Elena |
| Contributors | Eubanks, James |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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