期刊
PROGRESS IN LIPID RESEARCH
卷 50, 期 1, 页码 1-13出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.plipres.2010.10.006
关键词
Lysosomal phospholipase A(2) (LPLA(2)); 1-O-Acyl-ceramide synthase; Phospholipase A(2); Transacylase; Amiodarone; Cationic amphiphilic drugs; Lecithin-cholesterol acyltransferase (LCAT); LCAT like lysophospholipase (LLPL); Alveolar macrophages (AMs); Pulmonary surfactant; Phospholipidosis
资金
- NIH [1RO1 AR056991-01]
- Department of Veterans Affairs
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR056991] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK055823] Funding Source: NIH RePORTER
A phospholipase A(2) was identified from MDCK cell homogenates with broad specificity toward glycerophospholipids including phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol. The phospholipase has the unique ability to transacylate short chain ceramides. This phospholipase is calcium-independent, localized to lysosomes, and has an acidic pH optimum. The enzyme was purified from bovine brain and found to be a water-soluble glycoprotein consisting of a single peptide chain with a molecular weight of 45 kDa. The primary structure deduced from the DNA sequences is highly conserved between chordates. The enzyme was named lysosomal phospholipase A(2) (LPLA(2)) and subsequently designated group XV phospholipase A(2). LPLA(2) has 49% of amino acid sequence identity to lecithin-cholesterol acyltransferase and is a member of the alpha beta-hydrolase superfamily. LPLA2 is highly expressed in alveolar macrophages. A marked accumulation of glycerophospholipids and extensive lamellar inclusion bodies, a hallmark of cellular phospholipidosis, is observed in alveolar macrophages in LPLA(2)(-/-) mice. This defect can also be reproduced in macrophages that are exposed to cationic amphiphilic drugs such as amiodarone. In addition, older LPLA(2)(-/-) mice develop a phenotype similar to human autoimmune disease. These observations indicate that LPLA(2) may play a primary role in phospholipid homeostasis, drug toxicity, and host defense. Published by Elsevier Ltd.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据