title: The effects of aging on pulmonary oxidative damage, protein nitration, and extracellular superoxide dismutase down-regulation during systemic inflammation.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Marlene E
authors.initials: ME
authors.lastname: Starr
authors.forename: Junji
authors.initials: J
authors.lastname: Ueda
authors.forename: Shoji
authors.initials: S
authors.lastname: Yamamoto
authors.forename: B Mark
authors.initials: BM
authors.lastname: Evers
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saito
mesh_terms: D000375:Aging; D000818:Animals; D015153:Blotting, Western; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D019446:Endotoxemia / Q000378:metabolism / Q000473:pathology*; D005110:Extracellular Space / Q000201:enzymology*; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000633:toxicity; D055370:Lung Injury / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009566:Nitrates / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D009566:Nitrates; D012333:RNA, Messenger; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase