TY - JOUR

T1 - Apolipoprotein A-1 (apoA-1) deposition in, and release from, the enterocyte brush border

T2 - a possible role in transintestinal cholesterol efflux (TICE)?

AU - Danielsen, E Michael

AU - Hansen, Gert H

AU - Rasmussen, Karina

AU - Niels-Christiansen, Lise-Lotte

AU - Frenzel, Franz Bo

N1 - Copyright © 2011 Elsevier B.V. All rights reserved.

PY - 2012/3

Y1 - 2012/3

N2 - Transintestinal cholesterol efflux (TICE) has been proposed to represent a non-hepatobiliary route of cholesterol secretion directly "from blood to gut" and to play a physiologically significant role in excretion of neutral sterols, but so far little is known about the proteins involved in the process. We have previously observed that apolipoprotein A-1 (apoA-1) synthesized by enterocytes of the small intestine is mainly secreted apically into the gut lumen during fasting where its assembly into chylomicrons and basolateral discharge is at a minimal level. In the present work we showed, both by immunomicroscopy and subcellular fractionation, that a fraction of the apically secreted apoA-1 in porcine small intestine was not released from the cell surface but instead deposited in the brush border. Cholesterol was detected in immunoisolated microvillar apoA-1, and it was partially associated with detergent resistant membranes (DRMs), indicative of localization in lipid raft microdomains. The apolipoprotein was not readily released from microvillar vesicles by high salt or by incubation with phosphatidylcholine-specific phospholipase C or trypsin, indicating a relatively firm attachment to the membrane bilayer. However, whole bile or taurocholate efficiently released apoA-1 at low concentrations that did not solubilize the transmembrane microvillar protein aminopeptidase N. Based on these findings and the well known role played by apoA-1 in extrahepatic cellular cholesterol removal and reverse cholesterol transport (RCT), we propose that brush border-deposited apoA-1 in the small intestine acts in TICE by mediating cholesterol efflux into the gut lumen.

AB - Transintestinal cholesterol efflux (TICE) has been proposed to represent a non-hepatobiliary route of cholesterol secretion directly "from blood to gut" and to play a physiologically significant role in excretion of neutral sterols, but so far little is known about the proteins involved in the process. We have previously observed that apolipoprotein A-1 (apoA-1) synthesized by enterocytes of the small intestine is mainly secreted apically into the gut lumen during fasting where its assembly into chylomicrons and basolateral discharge is at a minimal level. In the present work we showed, both by immunomicroscopy and subcellular fractionation, that a fraction of the apically secreted apoA-1 in porcine small intestine was not released from the cell surface but instead deposited in the brush border. Cholesterol was detected in immunoisolated microvillar apoA-1, and it was partially associated with detergent resistant membranes (DRMs), indicative of localization in lipid raft microdomains. The apolipoprotein was not readily released from microvillar vesicles by high salt or by incubation with phosphatidylcholine-specific phospholipase C or trypsin, indicating a relatively firm attachment to the membrane bilayer. However, whole bile or taurocholate efficiently released apoA-1 at low concentrations that did not solubilize the transmembrane microvillar protein aminopeptidase N. Based on these findings and the well known role played by apoA-1 in extrahepatic cellular cholesterol removal and reverse cholesterol transport (RCT), we propose that brush border-deposited apoA-1 in the small intestine acts in TICE by mediating cholesterol efflux into the gut lumen.

KW - Animals

KW - Antigens, CD13

KW - Apolipoprotein A-I

KW - Biological Transport, Active

KW - Cell Membrane

KW - Cholesterol

KW - Chylomicrons

KW - Enterocytes

KW - Humans

KW - Intestine, Small

KW - Microvilli

KW - Swine

KW - Type C Phospholipases

U2 - 10.1016/j.bbamem.2011.11.011

DO - 10.1016/j.bbamem.2011.11.011

M3 - Journal article

C2 - 22119776

VL - 1818

SP - 530

EP - 536

JO - B B A - General Subjects

JF - B B A - General Subjects

SN - 0304-4165

IS - 3

ER -