Oxidative stress drives cellular senescence and iron uptake in airway epithelial cells

Background:

Accelerated ageing is associated with COPD, with more senescent cells found within the COPD lung. Elevated oxidative stress is observed in the COPD lung, as well as increased deposition of iron. Whether increased oxidative stress and increased intracellular iron are linked to senescence is unknown.

Methods:

Immunohistochemistry was performed on human lung sections from controls and COPD patients. Senescent cells were detected by senescence-associated-β-galactosidase (SA-β-Gal) staining. Iron and senescence markers were detected by western blot. Total intracellular iron was detected by atomic absorption spectroscopy (AAS).

Results:

Elevated levels of p16 and p21 staining were detected in COPD (N=12) lung sections compared to controls (p<0.05) (n=12). Oxidative stress (100 μM H₂0₂) induced cellular senescence in BEAS2B cells, with 30% of cells staining positively for SA-β-Gal (p<0.01). BEAS2B treated with H₂O₂ for 24 and 48 h increased p21 and reduced sirtuin-1 protein expression (p<0.05) (n=6), along with increased expression of ferritin and the transferrin receptor. Elevated intracellular iron and heme iron were found in cells treated with H₂O₂ in a time and concentration-dependent manner (P<0.01) (n=7). However, there was no increase in matrix-specific mitochondrial iron (n=6).

Conclusion:

Increased levels of senescence markers and iron uptake proteins, along with total intracellular iron are seen in cells exposed to oxidative stress. These data are the first linking oxidative stress-induced senescence and iron uptake in airway epithelial cells. However, more work is needed to elucidate whether the uptake of iron induces senescence or is a consequence of senescence.