Nozik-Grayck E, Dieterle C S, Piantadosi C A, Enghild J J, Oury T D
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA.
Am J Physiol Lung Cell Mol Physiol. 2000 Nov;279(5):L977-84. doi: 10.1152/ajplung.2000.279.5.L977.
Extracellular superoxide dismutase (EC-SOD), the only known enzymatic scavenger of extracellular superoxide, may modulate reactions of nitric oxide (NO) in the lungs by preventing reactions between superoxide and NO. The regulation 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 tension and NO in the neonatal lung. This study characterizes rabbit EC-SOD and investigates the developmental regulation of EC-SOD activity, protein expression, and localization. Purified rabbit EC-SOD was found to have several unique biochemical attributes distinct from EC-SOD in other species. Rabbit lung EC-SOD contains predominantly uncleaved subunits that do not form disulfide-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 after gestation. In addition, the enzyme is localized intracellularly in preterm and term rabbit lungs. Secretion of active EC-SOD into the extracellular compartment increases with age. The changes in EC-SOD localization and activity have implications for the neonatal pulmonary response to oxidative stress and the biological activity of NO at birth.
细胞外超氧化物歧化酶（EC-SOD）是唯一已知的细胞外超氧化物酶促清除剂，它可能通过阻止超氧化物与一氧化氮（NO）之间的反应来调节肺部一氧化氮的反应。尚未在发育中的肺中研究EC-SOD的调节作用。我们假设EC-SOD在新生儿肺对氧张力增加和NO的反应中起关键作用。本研究对兔EC-SOD进行了表征，并研究了EC-SOD活性、蛋白质表达和定位的发育调节。发现纯化的兔EC-SOD具有几种与其他物种的EC-SOD不同的独特生化特性。兔肺EC-SOD主要包含未切割的亚基，这些亚基不会形成二硫键连接的二聚体。亚基间二硫键的缺乏可能导致兔肺中肝素亲和力降低和EC-SOD含量降低。兔肺中的EC-SOD活性在出生前较低，妊娠后不久会增加。此外，该酶在早产和足月兔肺中定位于细胞内。随着年龄的增长，活性EC-SOD向细胞外区室的分泌增加。EC-SOD定位和活性的变化对新生儿肺对氧化应激的反应以及出生时NO的生物学活性具有重要意义。
