| Autor: |
Pergande MR; Department of Chemistry, University of Illinois at Chicago, Chicago, Illinois 60607, United States., Amoroso VG; Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois 60607, United States., Nguyen TTA; Department of Chemistry, University of Illinois at Chicago, Chicago, Illinois 60607, United States., Li W; Department of Chemistry, University of Illinois at Chicago, Chicago, Illinois 60607, United States., Vice E; Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois 60607, United States., Park TJ; Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois 60607, United States.; Laboratory for Integrative Neuroscience, University of Illinois at Chicago, Chicago, Illinois 60607, United States., Cologna SM; Department of Chemistry, University of Illinois at Chicago, Chicago, Illinois 60607, United States.; Laboratory for Integrative Neuroscience, University of Illinois at Chicago, Chicago, Illinois 60607, United States. |
| Abstrakt: |
Naked mole-rats (NMRs) are a long-lived animal that do not develop age-related diseases including neurodegeneration and cancer. Additionally, NMRs have a profound ability to consume reactive oxygen species (ROS) and survive long periods of oxygen deprivation. Here, we evaluated the unique proteome across selected brain regions of NMRs at different ages. Compared to mice, we observed numerous differentially expressed proteins related to altered mitochondrial function in all brain regions, suggesting that the mitochondria in NMRs may have adapted to compensate for energy demands associated with living in a harsh, underground environment. Keeping in mind that ROS can induce polyunsaturated fatty acid peroxidation under periods of neuronal stress, we investigated docosahexaenoic acid (DHA) and arachidonic acid (AA) peroxidation under oxygen-deprived conditions and observed that NMRs undergo DHA and AA peroxidation to a far less extent compared to mice. Further, our proteomic analysis also suggested enhanced peroxisome proliferator-activated receptor (PPAR)-retinoid X receptor (RXR) activation in NMRs via the PPARα-RXR and PPARγ-RXR complexes. Correspondingly, we present several lines of evidence supporting PPAR activation, including increased eicosapetenoic and omega-3 docosapentaenoic acid, as well as an upregulation of fatty acid-binding protein 3 and 4, known transporters of omega-3 fatty acids and PPAR activators. These results suggest enhanced PPARα and PPARγ signaling as a potential, innate neuroprotective mechanism in NMRs. |
