Identification and characterization of rodent ABCA1 in isolated type II pneumocytes.
ATP-binding cassette transporter A1 (ABCA1) promotes transfer of cholesterol and phospholipid from cells to lipid-free serum apolipoproteins. ABCA1 mRNA and protein expression in primary cultures of rodent type II cells was sensitive to upregulation with 5 microM 9-cis-retinoic acid (9cRA) and 6.2 microM 22-hydroxycholesterol (22-OH). The increase in ABCA1 protein levels was time dependent and was maximal after 16 h of exposure to 9cRA + 22-OH. Inducible ABCA1 was also found in transformed cell lines of lung origin: WI38/VA13, A549, and NIH-H441 cells. Stimulation of ABCA1 in rat type II cells by 9cRA + 22-OH resulted in a four- or fivefold enhancement of efflux of radioactive phospholipid or cholesterol, respectively, from the pneumocytes to apolipoprotein AI (apo AI), whereas cAMP (0.3 mM) had no effect. ABCA1-mediated lipid efflux to apo AI was independent of the surfactant secretion pathway, inasmuch as upregulation of ABCA1 resulted in a reduction of secretagogue-stimulated surfactant phospholipid release. These studies demonstrate the presence of functional ABCA1 in type II cells from the lung.
Bortnick
Anna E
AE
Institute for Environmental Medicine, University of Pennsylvania, 1 John Morgan Bldg., 36th and Hamilton Walk, Philadelphia, PA 19104-6068, USA.
Favari
Elda
E
Tao
Jian-Qin
JQ
Francone
Omar L
OL
Reilly
Muredach
M
Zhang
Yuzhen
Y
Rothblat
George H
GH
Bates
Sandra R
SR
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000077556:Alitretinoin; D000818:Animals; D016632:Apolipoprotein A-I / Q000494:pharmacology; D002461:Cell Line, Transformed; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology; D015854:Up-Regulation
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D006888:Hydroxycholesterols; D010743:Phospholipids; D012333:RNA, Messenger; C003585:22-hydroxycholesterol; D000077556:Alitretinoin; D014212:Tretinoin; D002784:Cholesterol