Molecular responses to hyperoxia in vivo: relationship to increased tolerance in aged rats.
In this study, we have used the rat model of hyperoxia to examine the molecular responses to oxidative stress in lung. We show that in addition to the antioxidant enzyme manganese superoxide dismutase, expression of a variety of stress-responsive genes including heme oxygenase-1, c-fos, c-jun, CAAT-enhancer binding protein (C/EBP)-beta, and C/EBP-delta were increased after hyperoxia. Increased c-fos, c-jun, C/EBP-beta, and C/EBP-delta mRNA expression was correlated with increased DNA binding activity of the transcription factor complexes activator protein 1 and C/EBP in tissue lysates. Because oxidative damage plays an important role in the aging process and little is known about the susceptibility of aged rats to hyperoxia, we also examined the relative tolerance of old rats to hyperoxia. Surprisingly, we observed that aged rats exhibit greater tolerance to hyperoxic stress than young rats. Old rats exhibited decreased arterial oxygen tension when compared to young rats after hyperoxia exposure. This increased tolerance coincided with decreased albumin levels in bronchoalveolar lavage and the delayed onset of activation of transcription factors and expression of oxidative stress-inducible genes in old rats. Transcription factor and stress-response gene activation may serve as useful molecular markers for oxidant lung injury.
Choi
A M
AM
Gene Expression and Aging Section, National Institute on Aging, Baltimore, Maryland, USA.
Sylvester
S
S
Otterbein
L
L
Holbrook
N J
NJ
D000375:Aging / Q000502:physiology*; D000418:Albumins / Q000032:analysis; D000818:Animals; D001483:Base Sequence; D001784:Blood Gas Analysis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics; D005786:Gene Expression Regulation; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis; D018496:Hyperoxia / Q000378:metabolism*; D008168:Lung / Q000502:physiology*; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics; D018384:Oxidative Stress / Q000502:physiology*; D010100:Oxygen / Q000097:blood; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D013482:Superoxide Dismutase / Q000032:analysis; D016019:Survival Analysis; D018808:Transcription Factor AP-1 / Q000032:analysis; D015533:Transcriptional Activation
D000418:Albumins; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D006419:Heme Oxygenase (Decyclizing); D013482:Superoxide Dismutase; D010100:Oxygen