Systemic inflammatory response syndrome (SIRS), a serious clinical condition characterized by whole-body inflammation, is particularly threatening for elderly patients, who suffer much higher mortality rates than the young. A major pathological consequence of SIRS is acute lung injury caused by neutrophil-mediated oxidative damage. Previously, we reported an increase in protein tyrosine nitration (a marker of oxidative/nitrosative damage) and a decrease in the antioxidant enzyme extracellular superoxide dismutase (EC-SOD) in the lungs of young mice during endotoxemia-induced SIRS. Here we demonstrate that during endotoxemia, down-regulation of EC-SOD is significantly more profound and prolonged, whereas up-regulation of iNOS is augmented, in aged compared to young mice. Aged mice also showed 2.5-fold higher protein nitration levels, compared to young mice, with particularly strong nitration in the pulmonary vascular endothelium during SIRS. Additionally, by two-dimensional gel electrophoresis, Western blotting, and mass spectrometry, we identified proteins that show increased tyrosine nitration in age- and SIRS-dependent manners; these proteins (profilin-1, transgelin-2, LASP 1, tropomyosin, and myosin) include components of the actin cytoskeleton responsible for maintaining pulmonary vascular permeability. Reduced EC-SOD in combination with increased oxidative/nitrosative damage and altered cytoskeletal protein function due to tyrosine nitration may contribute to augmented lung injury in the aged with SIRS.
|Number of pages||10|
|Journal||Free Radical Biology and Medicine|
|State||Published - Jan 15 2011|
Bibliographical noteFunding Information:
The authors thank Dr. John E. Wiktorowicz, Mrs. Susan J. Stafford, and Dr. Zheng Wu of the Biomolecular Resource Facility at the University of Texas Medical Branch for technical advice and assistance with the 2D gel experiments and analysis. The authors also thank Dr. James D. Crapo at the National Jewish Medical and Research Center for providing the anti-EC-SOD antibody and Dr. Michael B. Reid of the Department of Physiology at the University of Kentucky for his thoughtful advice and critique of the experimental data. This work was supported by National Institutes of Health Grant RO1-AG025908. Additional support came from the UTMB, Claude D. Pepper, Older Americans Independence Center, and NIH P30A6024832.
- Lung injury
- Oxidative damage
ASJC Scopus subject areas
- Physiology (medical)