A superoxide-driven redox state promotes geroconversion and resistance to senolysis in replication-stress associated senescence.

ABSTRACT: Using S-phase synchronized RPE1-hTERT cells exposed to the DNA damaging agent, methyl methanesulfonate, we show the existence of a redox state associated with replication stress-induced senescence termed senescence-associated redox state (SA-redox state). SA-redox state is characterized by its reactivity with superoxide-sensing fluorescent probes such as dihydroethidine, lucigenin and mitosox and peroxynitrite or hydroxyl radical sensing probe hydroxyphenyl fluorescein (HPF) but not the hydrogen peroxide (H₂O₂) reactive fluorescent probe CM-H₂DCFDA. Measurement of GSH and GSSH also reveals that SA-redox state mitigates the level of total GSH rather than oxidizes GSH to GSSG. Moreover, supporting the role of superoxide (O₂^.-) in the SA-

SUBMITTER: Luo L 

PROVIDER: S-EPMC10265521 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature