Maturational differences in hyperoxic AP-1 activation in rat lung

Immature organisms (neonates; <12 h old) have vastly differing responses to hyperoxic injury than adults. A common feature of hyperoxic gene regulatio n is involvement of activator protein (AP)-1. We evaluated lung AP-1 bindin g as well as that of the AP-1 subunit proteins c-Fos, c-Jun, phosphorylated c-Jun, Jun B, and Jun D after exposure to >95% O-2 for 3 days. Unlike adul ts, neonates showed no increased AP-1 binding in hyperoxia despite a high a ffinity of the AP-1 binding complexes for phosphorylated c-Jun and Jun D as demonstrated by supershift of these antibodies with the AP-1 complexes. Mo reover, neonatal lungs exhibited two distinguishable AP-1 binding complexes , whereas adult lungs had one. In neonates, sequential immunoprecipitation revealed that the lower AP-1 complex was composed of proteins from both the Fos and Jun families, whereas the upper complex consisted of Jun family pr oteins, with predominance of Jun D. In adults, the single AP-1 complex appe ared to involve other Fos or non-Fos or non-Jun family proteins as well. Ne onatal lungs showed a higher level of Jun B and Jun D immunoreactive protei ns in both air and hyperoxia compared with those in adult lungs. These resu lts suggest that significant maturational differences in lung AP-1 complexe s exist and that these may explain transcriptional differences in hyperoxic gene regulation.