Identification and characterization of a lysophosphatidylcholine acyltransferase in alveolar type II cells
Identification and characterization of a lysophosphatidylcholine acyltransferase in alveolar type II cells
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DOI：
10.1073/pnas.0604946103
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发表时间：
2006-08-01
影响因子：
11.1
通讯作者：
Shannon, John M.
中科院分区：
文献类型：
--
作者：
Chen, Xueni;Hyatt, Brian A.;Shannon, John M.
肺表面活性物质是由肺泡11型细胞产生和分泌的脂质和蛋白质的复合物，其在气-液界面处提供低表面张力。在肺中提供低表面张力的主要磷脂是二棕榈酰磷脂酰胆碱。二棕榈酰磷脂酰胆碱在很大程度上是通过磷脂酰胆碱（PC）重塑合成的，溶血磷脂酰胆碱（lysoPC）酰基转移酶被认为在其合成中起关键作用。然而，这种酰基转移酶尚未被鉴定。我们已经克隆了全长大鼠和小鼠编码lysoPC酰基转移酶（LPCAT）的cDNA。LPCAT编码一个由535个氨基酸组成的蛋白质，分子量约为59 kDa，含有一个跨膜结构域和一个酰基转移酶结构域。当转染COS-7细胞和HEK 293细胞时，LPCAT显著增加lysoPC酰基转移酶活性。与lysoPA、lysoPI、lysoPS、lysoPE或lysoPG相比，LPCAT优选lysoPC作为底物，并且与油酰辅酶A相比，LPCAT优选棕榈酰辅酶A作为酰基供体。这种LPCAT优先在肺中表达，特别是在肺泡11型细胞内。胎肺和大鼠11型细胞中的表达与表面活性蛋白的表达相关。LPCAT在胎肺组织块中的表达对地塞米松和FGF敏感。KGF是培养的成人11型细胞中LPCAT表达的有效刺激物。我们推测，LPCAT在调节表面活性剂磷脂的生物合成中起着至关重要的作用，并建议了解LPCAT的调节将提供重要的洞察表面活性剂磷脂的生物合成。
Pulmonary surfactant is a complex of lipids and proteins produced and secreted by alveolar type 11 cells that provides the low surface tension at the air-liquid interface. The phospholipid most responsible for providing the low surface tension in the lung is dipalmitoylphosphatidylcholine. Dipalmitoylphosphatidylcholine is synthesized in large part by phosphatidylcholine (PC) remodeling, and a lysophosphatidylcholine (lysoPC) acyltransferase is thought to play a critical role in its synthesis. However, this acyltransferase has not yet been identified. We have cloned full-length rat and mouse cDNAs coding for a lysoPC acyltransferase (LPCAT). LPCAT encodes a 535-aa protein of approximate to 59 kDa that contains a transmembrane domain and a putative acyltransferase domain. When transfected into COS-7 cells and HEK293 cells, LPCAT significantly increased lysoPC acyltransferase activity. LPCAT preferred lysoPC as a substrate over lysoPA, lysoPI, lysoPS, lysoPE, or lysoPG and prefers palmitoyl-CoA to oleoyl-CoA as the acyl donor. This LPCAT was preferentially expressed in the lung, specifically within alveolar type 11 cells. Expression in the fetal lung and in rat type 11 cells correlated with the expression of the surfactant proteins. LPCAT expression in fetal lung explants was sensitive to dexamethasone and FGFs. KGF was a potent stimulator of LPCAT expression in cultured adult type 11 cells. We hypothesize that LPCAT plays a critical role in regulating surfactant phospholipid biosynthesis and suggest that understanding the regulation of LPCAT will offer important insight into surfactant phospholipid biosynthesis.