ABCA3 as a lipid transporter in pulmonary surfactant biogenesis

被引:178
作者
Ban, Nobuhiro
Matsumura, Yoshihiro
Sakai, Hiromichi
Takanezawa, Yasukazu
Sasaki, Mayumi
Arai, Hiroyuki
Inagaki, Nobuya
机构
[1] Kyoto Univ, Dept Diabet & Clin Nutr, Grad Sch Med, Sakyo Ku, Kyoto 6068507, Japan
[2] JST, CREST, Kyoto 6068507, Japan
[3] JST, CREST, Akita 0108543, Japan
[4] Akita Univ, Sch Med, Dept Physiol, Akita 0108543, Japan
[5] Univ Tokyo, Dept Hlth Chem, Grad Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 1130033, Japan
关键词
D O I
10.1074/jbc.M611767200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
ABCA3 protein is expressed predominantly at the limiting membrane of the lamellar bodies in alveolar type 11 cells, and mutations in the ABCA3 gene cause lethal respiratory distress in newborn infants. To investigate the function of ABCA3 protein, we generated Abca3-deficient mice by targeting Abca3. Fullterm Abca3(-/-) newborn pups died within an hour after birth because of acute respiratory failure. Ultrastructural analysis revealed abnormally dense lamellar body-like organelles and no normal lamellar bodies in Abca3(-/-) alveolar type II cells. TLC and electrospray ionization mass spectrometry analyses of lipids in the pulmonary interstitium showed that phosphatidylcholine and phosphatidylglycerol, which contain palmitic acid and are abundant in normal surfactant lipids, were dramatically decreased in Abca3(-/-) lung. These findings indicate that ABCA3 plays an essential role in pulmonary surfactant lipid metabolism and lamellar body biogenesis, probably by transporting these lipids as substrates.
引用
收藏
页码:9628 / 9634
页数:7
相关论文
共 37 条
[1]   Human ABCA7 supports apolipoprotein-mediated release of cellular cholesterol and phospholipid to generate high density lipoprotein [J].
Abe-Dohmae, S ;
Ikeda, Y ;
Matsuo, M ;
Hayashi, M ;
Okuhira, K ;
Ueda, K ;
Yokoyama, S .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (01) :604-611
[2]   Simple and complex ABCR:: Genetic predisposition to retinal disease [J].
Allikmets, R .
AMERICAN JOURNAL OF HUMAN GENETICS, 2000, 67 (04) :793-799
[3]   LEVELS OF MESSENGER-RNAS CODING FOR LIPOGENIC ENZYMES IN RAT LUNG UPON FASTING AND REFEEDING AND DURING PERINATAL-DEVELOPMENT [J].
BATENBURG, JJ ;
WHITSETT, JA .
BIOCHIMICA ET BIOPHYSICA ACTA, 1989, 1006 (03) :329-334
[4]  
BLIGH EG, 1959, CAN J BIOCHEM PHYS, V37, P911
[5]   UTILIZATION OF GLYCOGEN FOR PHOSPHOLIPID-SYNTHESIS IN FETAL-RAT LUNG [J].
BOURBON, JR ;
RIEUTORT, M ;
ENGLE, MJ ;
FARRELL, PM .
BIOCHIMICA ET BIOPHYSICA ACTA, 1982, 712 (02) :382-389
[6]   ABCA3 mutations associated with pediatric interstitial lung disease [J].
Bullard, JE ;
Wert, SE ;
Whitsett, JA ;
Dean, M ;
Nogee, LM .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2005, 172 (08) :1026-1031
[7]   FETAL AND POSTNATAL-DEVELOPMENT OF THE LUNG [J].
BURRI, PH .
ANNUAL REVIEW OF PHYSIOLOGY, 1984, 46 :617-628
[8]  
CHANDER A, 1990, AM J PHYSIOL, V258, P241
[9]   Functional and trafficking defects in ATP binding cassette A3 mutants associated with respiratory distress syndrome [J].
Cheong, N ;
Madesh, M ;
Gonzales, LW ;
Zhao, M ;
Yu, K ;
Ballard, PL ;
Shuman, H .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (14) :9791-9800
[10]   TARGETED DISRUPTION OF THE SURFACTANT PROTEIN-B GENE DISRUPTS SURFACTANT HOMEOSTASIS, CAUSING RESPIRATORY-FAILURE IN NEWBORN MICE [J].
CLARK, JC ;
WERT, SE ;
BACHURSKI, CJ ;
STAHLMAN, MT ;
STRIPP, BR ;
WEAVER, TE ;
WHITSETT, JA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (17) :7794-7798