title: Dominant expression of ATP-binding cassette transporter-1 on basolateral surface of Caco-2 cells stimulated by LXR/RXR ligands.
abstract: ATP-binding cassette transporter-1 (ABCA1) is a cause of Tangier disease, which is a familial deficiency of plasma high density lipoproteins (HDL). This molecule is known to be expressed in the multiple tissues and organs including small intestines, liver, and macrophages in the blood vessels. Recent in vivo studies suggested that ABCA1 plays some roles in the flux of cholesterol in the intestines. One of the major questions to understand the roles of ABCA1 in the intestines is the expression pattern in the intestinal epithelial cells. To address this issue, we have investigated the expression and regulation of ABCA1 in Caco-2 cells cultured on Transwell as a model, especially focusing on possible polarized expression of ABCA1. The expression of ABCA1 was up-regulated during the differentiation and under the stimulation of LXR/RXR by the addition of 9-cis-retinoic acid (9-cis-RA) and 22-R-hydroxycholesterol (22-OH). Apolipoprotein-AI-mediated cholesterol efflux was dominant toward the basolateral side of polarized cells when stimulated by 9-cis-RA and 22-OH. The cell surface biotinylation experiment followed by Western blot analyses demonstrated a markedly dominant expression of ABCA1 on the basolateral surface, which was clearly confirmed by the confocal laser scanning microscopy. In conclusion, the present study demonstrates that ABCA1 is dominantly expressed on the basolateral surface of Caco-2 cells tested, suggesting that this molecule may play a role in the basolateral movement of cholesterol at least when stimulated by LXR/RXR ligands.
authors.affiliation: Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Ohama
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Hirano
authors.forename: Zhongyan
authors.initials: Z
authors.lastname: Zhang
authors.forename: Ryo
authors.initials: R
authors.lastname: Aoki
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Tsujii
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Nakagawa-Toyama
authors.forename: Kosuke
authors.initials: K
authors.lastname: Tsukamoto
authors.forename: Chiaki
authors.initials: C
authors.lastname: Ikegami
authors.forename: Akifumi
authors.initials: A
authors.lastname: Matsuyama
authors.forename: Masato
authors.initials: M
authors.lastname: Ishigami
authors.forename: Naohiko
authors.initials: N
authors.lastname: Sakai
authors.forename: Hisatoyo
authors.initials: H
authors.lastname: Hiraoka
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Ueda
authors.forename: Shizuya
authors.initials: S
authors.lastname: Yamashita
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsuzawa
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000096:biosynthesis*; D016632:Apolipoprotein A-I / Q000494:pharmacology; D001692:Biological Transport; D018938:Caco-2 Cells; D002454:Cell Differentiation; D002462:Cell Membrane / Q000737:chemistry; D016764:Cell Polarity; D002784:Cholesterol / Q000378:metabolism; D003106:Colon / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins; D006801:Humans; D008024:Ligands; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D018168:Receptors, Retinoic Acid / Q000819:agonists*; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000819:agonists*; D015854:Up-Regulation
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D004268:DNA-Binding Proteins; D008024:Ligands; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D002784:Cholesterol