Differential Regulation of the Extracellular CysteineCystine Redox State (EhCySS)‎ by Lung Fibroblasts from Young and Old Mice

الملخص EN

Aging is associated with progressive oxidation of plasma cysteine (Cys)/cystine (CySS) redox state, expressed as E h C y S S .

Cultured cells condition their media to reproduce physiological E h C y S S , but it is unknown whether aged cells produce a more oxidized extracellular environment reflective of that seen in vivo.

In the current study, we isolated primary lung fibroblasts from young and old female mice and measured the media E h C y S S before and after challenge with Cys or CySS.

We also measured expression of genes related to redox regulation and fibroblast function.

These studies revealed that old fibroblasts produced a more oxidizing extracellular E h C y S S than young fibroblasts and that old fibroblasts had a decreased capacity to recover from an oxidative challenge due to a slower rate of reduction of CySS to Cys.

These defects were associated with 10-fold lower expression of the Slc7a11 subunit of the xCT cystine-glutamate transporter.

Extracellular superoxide dismutase (Sod3) was the only antioxidant or thiol-disulfide regulating enzyme among 36 examined that was downregulated in old fibroblasts by more than 2-fold, but there were numerous changes in extracellular matrix components.

Thus, aging fibroblasts not only contribute to remodeling of the extracellular matrix but also have a profound effect on the extracellular redox environment.