Naked mole rats activate neuroprotective proteins during hypoxia. Issue 10 (23rd September 2019)

• Record Type: Journal Article
• Authors: Hawkins, Liam J.; Hadj‐Moussa, Hanane; Nguyen, Vu C.; Pamenter, Matthew E.; Storey, Kenneth B.
• Is Part Of: Journal of experimental zoology. Volume 331:Issue 10(2019)
• Page Start: 571
• Page End: 576
• Publication Date: 2019-09-23
• Subjects: Heterocephalus glaber -- HIF1α -- NFκB -- prosurvival; Zoology -- Periodicals; Zoology; Animal Population Groups -- physiology; Zoology; Electronic journals; Periodical; Periodicals; 590
• DOI: 10.1002/jez.2321
• Languages: English
• ISSNs: 2471-5646

Abstract

Abstract: Naked mole rats are a long‐lived animal model that age much like humans, but that can also withstand oxidative damage, cancer, neurodegenerative diseases, and severe hypoxic conditions, which is of particular interest to this study. The conditions of their underground burrows result in competition for oxygen consumption, yet despite this oxygen deprivation they emerge unscathed. To understand the mechanisms in place to facilitate neuronal preservation during hypoxia, we investigated the protein levels of well‐known cell‐stress factors. We found that under hypoxic conditions, nearly half of the proteins measured increased expression in brain, while only a few decreased. Under hypoxic conditions there appeared to be a HIF1α‐centered response, where HIF1α and its interactors carbonic anhydrase 9, CITED2, p21/CIP1, and NFκB1, among others, were upregulated. Concurrently, a hypoxia‐induced decrease of cytochrome c was consistent with decreased mitochondrial function and protection from apoptosis. The picture that emerges is one of neuroprotection, cell‐cycle arrest, and the promotion of antiapoptotic functions, all of which are consistent with conserving energy and maintaining neural integrity under low oxygen levels. These results suggest how this species may be poised to face hypoxia and contribute to its remarkable ability to deal with myriad of other damaging factors and sets the stage for future work on the neuroprotective facilitators we identified. Abstract : Central prosurvival protein changes observed in hypoxic naked mole rat brains. Research Highlight: HIF1α‐centered response in hypoxic naked mole rat brains was observed including increases in p21 and NFκB. Cell‐cycle arrest, antiapoptosis, and energy conservation all emerge as critical mechanisms for brain preservation during oxygen deprivation.