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Signal transduction of lung surfactant synthesis, transport, and secretion in alveolar type II cell

肺泡 II 型细胞中肺表面活性剂合成、转运和分泌的信号转导

基本信息

批准号：
10670566
负责人：
OSANAI Kazuhiro
金额：
$ 1.79万
依托单位：
Kanazawa Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670566/
关键词：
lung surfactant alveolar type II cell intracellular transport lamellar body brefeldin A

项目摘要

Lung surfactant, a mixture of lipids and apoproteins, is synthesized in alveolar type II cells and is essential substance for maintaining lung homeostasis. This research project has revealed followings. (1) Phosphatidylcholine, a major lipidcomponent of lung surfactant, is synthesized in endoplasmic reticulum, transported to and stored in lamellar bodies via the Golgi-independent pathway. In contrast, surfactant protein A, one of the four apoproteins, is synthesized in endoplasmic reticulum, transported to the Golgi and is glycosylated, and is constitutively secreted out of the cells. The secreted protein is endocytosed into alveolar type II cells and transported to lamellar bodies. (2) The research also identified and partially characterized an intracellular molecule of an approximately 110 kD molecular weight on a gel filtration chromatography, which induces surfactant exocytosis. (3) ADP-ribosylation of adenylate cyclase-associated heterotrimeic G protein by cholera toxin unexpectedly but strongly inhibits lung surfactant secretion. These results indicate that the postulated pathway of lung surfactant so far is wrong, and have brought new aspects of lung surfactant biology. (4) Furthermore, we have investigated effects of lung deflation and several agents on alveolar water clearance. Taken together, these findings will lead to better understanding of pathogenesis of acute respiratory failure and a novel therapeutic strategy.These results were published in medical journals, presented in medical meetings, and submitted to medical books. Especially, these papers published in American medical journals counted totally 11.295 of Impact Factor (Journal Citation Report, ISI).

肺表面活性物质是一种由脂质和载脂蛋白组成的混合物，由肺泡II型细胞合成，是维持肺内环境稳定的重要物质。该研究项目揭示了以下内容。(1)磷脂酰胆碱是肺表面活性物质的主要脂质成分，在内质网中合成，通过高尔基体非依赖性途径转运并储存在板层体中。相反，表面活性蛋白A，四种脱辅基蛋白之一，在内质网中合成，运输到高尔基体并被糖基化，并且组成性地分泌出细胞。分泌的蛋白被内吞入肺泡II型细胞并转运至板层体。(2)该研究还确定并部分表征了凝胶过滤色谱上分子量约为110 kD的细胞内分子，其诱导表面活性剂胞吐作用。(3)霍乱毒素对腺苷酸环化酶相关异三聚体G蛋白的ADP-核糖基化出乎意料地但强烈地抑制肺表面活性物质的分泌。这些结果表明，迄今为止假设的肺表面活性物质的途径是错误的，并带来了新的方面的肺表面活性物质的生物学。(4)此外，我们还研究了肺放气和几种药物对肺泡水清除的影响。这些发现将有助于更好地了解急性呼吸衰竭的发病机制和新的治疗策略。这些结果发表在医学期刊上，在医学会议上发表，并提交给医学书籍。其中，在美国医学期刊上发表的论文影响因子（Journal Citation Report，ISI）为11.295。