Secretion of extracellular superoxide dismutase in neonatal lungs

Extracellular superoxide dismutase (EC-SOD), the only known enzymatic scave nger of extracellular superoxide, may modulate reactions of nitric oxide (N O) in the lungs by preventing reactions between superoxide and NO. The regu lation of EC-SOD has not been examined in developing lungs. We hypothesize that EC-SOD plays a pivotal role in the response to increased oxygen tensio n and NO in the neonatal lung. This study characterizes rabbit EC-SOD and i nvestigates the developmental regulation of EC-SOD activity, protein expres sion, and localization. Purified rabbit EC-SOD was found to have several un ique biochemical attributes distinct from EC-SOD in other species. Rabbit l ung EC-SOD contains predominantly uncleaved subunits that do not form disul fide-linked dimers. The lack of intersubunit disulfide bonds may contribute to the decreased heparin affinity and lower EC-SOD content in rabbit lung. EC-SOD activity in rabbit lungs is low before birth and increases soon aft er gestation. In addition, the enzyme is localized intracellularly in prete rm and term rabbit lungs. Secretion of active EC-SOD into the extracellular compartment increases with age. The changes in EC-SOD localization and act ivity have implications for the neonatal pulmonary response to oxidative st ress and the biological activity of NO at birth.