Limitations to adaptive homeostasis in an hyperoxia-induced model of accelerated ageing.

ABSTRACT: The Nrf2 signal transduction pathway plays a major role in adaptive responses to oxidative stress and in maintaining adaptive homeostasis, yet Nrf2 signaling undergoes a significant age-dependent decline that is still poorly understood. We used mouse embryonic fibroblasts (MEFs) cultured under hyperoxic conditions of 40% O₂, as a model of accelerated ageing. Hyperoxia increased baseline levels of Nrf2 and multiple transcriptional targets (20S Proteasome, Immunoproteasome, Lon protease, NQO1, and HO-1), but resulted in loss of cellular ability to adapt to signaling levels (1.0 μM) of H₂O₂. In contrast, MEFs cultured at physiologically relevant conditions of 5% O₂ exhibited a transient induction of Nrf2 Phase II target genes and stress-protective e

SUBMITTER: Pomatto LCD 

PROVIDER: S-EPMC6479762 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature