Autophagy through XXXX and @entity21060 regulates oxidative stress-induced premature senescence in auditory cells.

@entity274 @entity21060 @entity3607 @entity10615 @entity5291
UNASSIGNED: The aim of this study was to determine whether autophagy and @entity21060 contribute to premature senescence in auditory cells. Incubating HEI-OC1 auditory cells with 5 mM @entity274 for 1 h induced senescence, as demonstrated by senescence-associated b-galactosidase (SA-b-gal) staining. @entity274 treatment significantly delayed population-doubling time, leaving cell viability unchanged. Furthermore, the proportion of SA-b-gal-positive cells significantly increased. Autophagy-related protein expression increased, with @entity10615 and LC3-II peaking 6 h and @entity3607 peaking 24 h after @entity274 treatment. The expression of these proteins decreased 48 h after treatment. Transmission electron microscopy revealed lipofuscin and aggregates within autolysosomes, which accumulated markedly in the cytoplasm of HEI-OC1 cells 48 h after treatment. Akt and P70S6 phosphorylation markedly decreased after @entity274 treatment, but @entity5291 phosphorylation significantly increased 48 h after treatment. After RNAi-mediated knockdown (KD) of @entity10615 and @entity21060 , @entity274 -treated cells displayed dense SA-b-gal staining. Also, premature senescence was significantly induced. These suggest that a negative feedback loop may exist between autophagy and @entity21060 signaling pathways in HEI-OC1 cells. In our model, oxidative stress-induced premature senescence occurred due to impaired autophagy function through @entity5291 phosphorylation. Our results also indicate that @entity21060 may regulate premature senescence in auditory cells in an autophagy-dependent and independent manner.
