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Oxidative Medicine and Cellular Longevity
Volume 2016, Article ID 1561305, 11 pages
Research Article

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

1Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY, USA
2Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, USA
3Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, USA
4Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, University of Louisville School of Medicine, Louisville, KY, USA
5Robley Rex Veterans Affairs Medical Center, Louisville, KY, USA

Received 5 May 2016; Accepted 7 August 2016

Academic Editor: Jean-Claude Lavoie

Copyright © 2016 Walter H. Watson et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Aging is associated with progressive oxidation of plasma cysteine (Cys)/cystine (CySS) redox state, expressed as . Cultured cells condition their media to reproduce physiological , 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 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 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.