Effect of glutathione on lung activator protein-1 activation and heme oxygenase-1 induction in the immature rat.
Differences in lung heme oxygenase-1 (HO-1) regulation have been demonstrated in newborn (<12 h old) and adult (>2 month old) rats after exposure to hyperoxia. Contrary to adults, neonates do not demonstrate increased lung HO-1 induction nor transcription factor activator protein-1 (AP-1) binding in hyperoxia. Because AP-1 activation can be posttranslationally modified by oxidants or reductants, we investigated whether differences in lung glutathione (GSH) content account for the maturational differences in AP-1 activation and subsequent HO-1 gene regulation after hyperoxia. Neonatal rats were injected with either 1-buthionine-[S,R] sulfoximine (BSO), diamide, or selenite during the 72-h hyperoxic exposure. Lung GSH content, glutathione disulfide (GSSG) content, AP-1 binding, and HO-1 mRNA were evaluated. The ratios of GSSG to GSH were used to reflect the GSH redox state in the lungs. Changes in lung GSSG/GSH ratio did not alter AP-1 binding but did increase HO-1 mRNA in neonates. These data suggest that the neonatal lung is relatively resistant to AP-1 activation and HO-1 induction by GSH perturbation.
Yang
Guang
G
Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94304, USA.
Shegog
Mychell L
ML
Dennery
Phyllis A
PA
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005978:Glutathione / Q000378:metabolism*; D019803:Glutathione Disulfide / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1; D018496:Hyperoxia / Q000378:metabolism; D066298:In Vitro Techniques; D008168:Lung / Q000201:enzymology*; D008297:Male; D010084:Oxidation-Reduction; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D018808:Transcription Factor AP-1; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D005978:Glutathione; D019803:Glutathione Disulfide