TY - JOUR
T1 - Dominant expression of ATP-binding cassette transporter-1 on basolateral surface of Caco-2 cells stimulated by LXR/RXR ligands
AU - Ohama, Tohru
AU - Hirano, Ken ichi
AU - Zhang, Zhongyan
AU - Aoki, Ryo
AU - Tsujii, Ken ichi
AU - Nakagawa-Toyama, Yumiko
AU - Tsukamoto, Kosuke
AU - Ikegami, Chiaki
AU - Matsuyama, Akifumi
AU - Ishigami, Masato
AU - Sakai, Naohiko
AU - Hiraoka, Hisatoyo
AU - Ueda, Kazumitsu
AU - Yamashita, Shizuya
AU - Matsuzawa, Yuji
N1 - Funding Information:
We thank Kyowa Hakko Kogyo Co. Ltd. for producing the Ab ABCA1 45–639 . This work was supported by research grants from Study Group of Molecular Cardiology (Japan), from Japan Heart Foundation (Japan), from Japan Heart Foundation/Pfizer Grant for Research on Hypertension and Vascular Metabolism (Japan), and from Tanabe Medical Frontier Conference (TMFC) (Japan) to K. Hirano. This work was supported by the International HDL Research Awards Program grant to S. Yamashita. This work was supported by grants-in-aid to S. Yamashita (No. 11557055 and No. 10671070) and K. Hirano (No. 13671191) from the Ministry of Education, Science, Sports and Culture of Japan.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
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U2 - 10.1016/S0006-291X(02)00853-7
DO - 10.1016/S0006-291X(02)00853-7
M3 - Article
C2 - 12176027
AN - SCOPUS:18644364016
VL - 296
SP - 625
EP - 630
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -