Lysosomal Phospholipase A2 in Lung DPPC

肺中的溶酶体磷脂酶 A2 DPPC

基本信息

批准号：
7329972
负责人：
Aron B. FISHER
金额：
$ 48.42万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-07-01 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7329972
关键词：
Active Sites Alveolar Antibodies Bos taurus Breeding Cattle Cells Complementary DNA Development Doctor of Medicine Doctor of Philosophy Enzymes Exhibits Gene Targeting Goals Grant Human Hydrolase Immunoprecipitation Knock-out Length Lipid Binding Localized Lung Lysosomes Metabolism Molecular Mouse Protein Mus Mutagenesis Names Organ Pathway interactions Peroxidase Peroxidases Phospholipase A2 Phospholipids Phosphorylation Physiological Platelet Activating Factor Play Positioning Attribute Principal Investigator Property Proteins Publishing Pulmonary Surfactants Range Rat Protein Rattus Recombinant Proteins Regulation Research Research Personnel Role Structure Structure of parenchyma of lung Structure-Activity Relationship Study models Time Tissues Transgenic Mice Transgenic Organisms Western Blotting abstracting age related alveolar lamellar body deacylation immunocytochemistry in vivo novel peroxiredoxin pneumocyte polyclonal antibody professor protein protein interaction surfactant

项目摘要

Principal Investigator: Fisher. Aron B. PROJECT #6: LYSOSOMAL PHOSPHOLIPASE A2 IN LUNG DPPC METABOLISM Name eraCommons Role on Project Affiliation Aron B. Fisher, M.D. abfifem Responsible Invest. Univ. Penn Sheldon I. Feinstein, Ph.D. feinsteins Co-Investigator Univ. Penn Yefim Manevich, Ph.D. Co-Investigator Univ. Penn Brian Bahnson, Ph.D. Participating Univ. Del Investigator Tomo Oe, Ph.D. Participating Univ. Penn Investigator Position Professor and Director Sr. Research Invest. Sr. Research Invest. Associate Professor Res. Asst. Professor ABSTRACT This project will evaluate the properties and physiological role of a novel phospholipase A2 (aiPLA2) that is one of the enzymatic activities of the protein called peroxiredoxin 6. We have isolated the protein from rat and bovine lungs, have identified the full length cDNA for the human, rat, mouse and bovine enzyme, have generated recombinant protein, and have developed a panel of antibodies that are effective for western blotting, immunoprecipitation and immunocytochemistry. aiPLA2 is Ca++-independent, shows maximal activity at pH 4, and represents a lysosomal-type PLA2. During the present period of grant support, we have shown that aiPLA2: 1) plays a major role in degradation of internalized alveolar DPPC; 2) provides substrate for the reacylation pathway of DPPC synthesis; 3) activity is regulated through protein-protein interactions with SP-A; 4) is localized in lung to lamellar bodies and lysosomes; 5) is activated by phosphorylation; and 6) its expression is developmental^ regulated and hormonally responsive. Specific Aim 1 will study models of under- and over-expression of aiPLA2 (knockout and transgenic mice) in order to evaluate the physiologic role of the enzyme in DPPC degradation and synthesis using isolated cells, the isolated perfused lung, and in vivo studies. Time-related (aging) changes in lung phospholipid content will be determined. Specific Aim 2 will evaluate the structure-function relationships for aiPLA2 activity utilizing

首席研究员：费舍尔。 Aron B. 项目＃6：肺DPPC代谢中的溶酶体磷脂酶A2 名称Eracommons在项目隶属关系中的角色 Aron B. Fisher，医学博士Abfifem负责投资。大学。宾夕法尼亚 Sheldon I. Feinstein博士feinsteins共同评估器大学。宾夕法尼亚 Yefim Manevich博士共同投资者大学。宾夕法尼亚 Brian Bahnson博士参加大学。 del 研究者 Tomo OE，博士参加大学。宾夕法尼亚研究者位置教授兼董事高级研究投资。高级研究投资。副教授 res。助理。教授抽象的该项目将评估新型磷脂酶A2（AIPLA2）的特性和生理作用，这是一个在称为过氧蛋白6的蛋白质的酶促活性中。我们已经从大鼠中分离了蛋白质牛肺已经确定了人，大鼠，小鼠和牛酶的全长cDNA 产生的重组蛋白，并开发了一组对西部有效的抗体印迹，免疫沉淀和免疫细胞化学。 AIPLA2是Ca ++独立的，显示了最大活性在pH 4处，代表溶酶体型PLA2。在目前的赠款支持期间，我们已经表明 AIPLA2：1）在内部化肺泡DPPC的降解中起着重要作用； 2）为 DPPC合成的重新鉴定途径； 3）通过与SP-A的蛋白质蛋白质相互作用来调节活性； 4）位于肺部与层状体和溶酶体； 5）被磷酸化激活； 6）它表达是发育^的调节和荷尔蒙响应式的。特定目标1将研究 AIPLA2（基因敲除和转基因小鼠）的低表达，以评估生理角色使用分离的细胞，分离的灌注肺和体内的DPPC降解和合成中的酶的酶研究。将确定肺磷脂含量的时间相关（衰老）变化。具体目标2将评估利用AIPLA2活动的结构功能关系