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 addit ion to the antioxidant enzyme manganese superoxide dismutase, expressi on 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-d elta were increased after hyperoxia. Increased c-fos, c-jun, C/EBP-bet a, and C/EBF-delta mRNA expression was correlated with increased DNA b inding activity of the transcription factor complexes activator protei n 1 and C/EBP in tissue lysates. Because oxidative damage plays an imp ortant role in the aging process and little is known about the suscept ibility of aged rats to hyperoxia, we also examined the relative toler ance of old rats to hyperoxia. Surprisingly, we observed that aged rat s exhibit greater tolerance to hyperoxic stress than young rats. Old r ats exhibited decreased arterial oxygen tension when compared to young rats after hyperoxia exposure. This increased tolerance coincided wit h decreased albumin levels in bronchoalveolar lavage and the delayed o nset of activation of transcription factors and expression of oxidativ e stress-inducible genes in old rats. Transcription factor and stress- response gene activation may serve as useful molecular markers for oxi dant lung injury.