CALCIUM-DEPENDENT PHOSPHOLIPID-BINDING PROTEINS AS RELATED TO LUNG DEVELOPMENT

支气管肺发育不良是呼吸窘迫的主要后遗症 综合征(RDS)早产儿。尽管很明显，RDS主要是 由于肺表面活性物质的缺乏，其发生机制 石油日产量的定义仍然不明确。最近，我们提纯了两个钙依赖的 兔肺磷脂结合蛋白(PLBP)。这些蛋白质是 见于肺泡II型细胞和肺泡的衬里层及更大 他们优先将囊泡融合到表面活性物质膜上。 我们的观察表明，PLBP可能在 表面活性物质的生物生成。因此，如果这些蛋白质有任何缺陷 在肺部，这可能与RDS和/或BPD的发生有关。 这些假设将通过以下拟议的实验来检验：(1) 测定发育中肺中的PLBPs并研究类固醇的影响 和高氧对这些蛋白质的影响；(2)研究 PLBP与RDS和BPD发展的关系；(3) PLBPs的体外蛋白质合成及翻译后修饰 更好地理解这些分子的结构与功能的关系 (4)研究PLBP在II型细胞中的作用和调控 与表面活性物质代谢的关系；(5)研究表面活性物质的作用机制 PLBPS与钙离子、磷脂和表面活性物膜的结合 更好地了解蛋白质的结合作用和蛋白质的 优先与表面活性剂膜结合。这些研究将提供 了解肺与肺的关系的重要信息 PLBPS、表面活性物质的生物发生以及RDS和BPD的发展。数据来自 这些研究也可能被证明对设计RDS的新治疗方法有用 和BPD。

Bronchopulmonary dysplasia is the major sequela of respiratory distress syndrome (RDS) premature infants. Although it is clear that RDS is mainly due to the deficiency of lung surfactant, the mechanisms of the development of BPD remain poorly defined. Recently, we purified two Ca2+ - dependent phospholipid binding proteins (PLBPs) from rabbit lung. These proteins are found in alveolar type II cells and the lining layers of alveoli and larger airways, and they preferentially fuse vesicles to surfactant membranes. Our observations suggest that PLBPs may play an important role in surfactant biogenesis. Thus, if there is any deficiency of these proteins in lung, this may be associated with the development of RDS and/or BPD. These hypotheses will be tested by the following proposed experiments: (1) determine PLBPs in developing lungs and investigate the effects of steroids and hyperoxia on these proteins during lung growth; (2) investigate the relationship between PLBPs and the development of RDS and BPD; (3) study in vitro protein synthesis and post-translation modifications of PLBPs for better understanding the structure-function relationships of these proteins; (4) investigate the role and regulation of PLBPs in type II cells in relationship to surfactant metabolism; (5) study the mechanisms of binding of PLBPs with Ca2+, phospholipids and surfactant membranes for better understanding the protein's binding actions and the protein's preferential binding with surfactant membranes. These studies will provide important information for understanding the relationship between lung PLBPS, surfactant biogenesis and the development of RDS and BPD. Data from these studies may also prove useful for designing novel treatment for RDS and BPD.