Overexpression of Apolipoprotein A-iv Enhances Lipid Secretion in Ipec-1 Cells by Increasing Chylomicron Size.
From: Children’s Foundation Research Center at Le Bonheur Children’s Medical Center and Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee 38103, USA.
The Journal of biological chemistry
- Publish Date: Feb 2006
- ISSN: 0021-9258
- Volume: 281
- Issue: 6
- Pages: 3473-83
- Medium: Print
- Language: English
- Citation (JAMA): Lu Song, Yao Ying, Cheng Xiangying, et al. Overexpression of Apolipoprotein A-iv Enhances Lipid Secretion in Ipec-1 Cells by Increasing Chylomicron Size.. J. Biol. Chem. Feb 2006;281:3473-83
Abstract
Intestinal apolipoprotein A-IV expression is highly regulated by dietary lipid in newborn swine, suggesting a role in lipid absorption. Constitutive overexpression of apoA-IV in newborn swine enterocytes enhances basolateral secretion of triacylglycerol (TG) in TG-rich lipoproteins 4.9-fold (Lu, S., Yao, Y., Meng, S., Cheng, X., and Black, D. D.(2002) J. Biol. Chem. 277, 31929-31937). To investigate the mechanism of this enhancement, IPEC-1 cells were transfected with a tetracycline-regulatable expression system (Tet-On). In cells incubated with oleic acid, a dose response relationship was observed between medium doxycycline concentration and basolateral apoA-IV and TG secretion. Similarly regulated expression of apoA-I did not enhance lipid secretion. The mean diameter of TG-rich lipoproteins secreted from doxycycline-treated cells was larger than from untreated cells (87.0 nm versus 53.4 nm). Basolateral apoB secretion decreased. Using the same expression system, full-length human apoA-IV (376 amino acids); a “pig-like” human apoA-IV, lacking the C-terminal EQQQ repeats (361 amino acids); and a “chicken-like” apoA-IV, further truncated to 343 amino acids, were expressed in IPEC-1 cells. With increasing protein secretion, cells expressing the full-length human apoA-IV displayed a 2-fold increase in TG secretion; in sharp contrast, cells expressing the pig-like human apoA-IV displayed a 25-fold increase in TG secretion and a 27-fold increase in lipoprotein diameter. When human apoA-IV was further truncated to yield a chicken-like protein, TG secretion was inhibited. We conclude that overexpression of swine apoA-IV enhances basolateral TG secretion in a dose-dependent manner by increasing the size of secreted lipoproteins. These data suggest that the region in the human apoA-IV protein from residues 344 to 354 is critical to its ability to enhance lipid secretion, perhaps by enabling the packaging of additional core TG into chylomicron particles. The EQQQ-rich region may play an inhibitory or modulatory role in chylomicron packaging in humans.
Mesh Headings (Keywords): Amino Acid Sequence, Animals, Animals, Newborn, Apolipoproteins, Apolipoproteins A, Blotting, Western, Cell Line, Chickens, Chylomicrons, Cloning, Molecular, DNA, Complementary, Dose-Response Relationship, Drug, Doxycycline, Electrophoresis, Polyacrylamide Gel, Humans, Immunoprecipitation, Intestines, Lipid Metabolism, Lipids, Lipoproteins, Microscopy, Electron, Microscopy, Electron, Transmission, Molecular Sequence Data, Mutation, Oleic Acid, Protein Structure, Tertiary, RNA, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, Swine, Tetracycline, Trans-Activation (Genetics), Triglycerides
Check for Full Text / PubMed Unique Identifier (PMID): 16338933
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