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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Mulya, Anny Seo, Jeongmin Brown, Amanda L. Gebre, Abraham K. Boudyguina, Elena Shelness, Gregory S. Parks, John S. |
| Description | Country affiliation: United States Author Affiliation: Mulya A ( Department of Pathology/Section on Lipid Sciences, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA.) |
| Abstract | Apolipoprotein M (apoM) is a novel apolipoprotein that is reportedly necessary for pre beta HDL formation; however, its detailed function remains unknown. We investigated the biogenesis and properties of apoM and its effects on the initial steps of nascent pre beta HDL assembly by ABCA1 in HEK293 cells. Transiently transfected apoM was localized primarily in the endomembrane compartment. Pulse-chase analyses demonstrated that apoM is inefficiently secreted, relative to human serum albumin, and that approximately 50% remains membrane-associated after extraction with sodium carbonate, pH 11.5. To investigate the role of apoM in nascent pre beta HDL formation, ABCA1-expressing or control cells, transfected with empty vector, apoM, or C-terminal epitope-tagged apoM (apoM-C-FLAG), were incubated with (125)I-apoA-I for 24 h. Conditioned media were harvested and fractionated by fast-protein liquid chromatography (FPLC) to monitor HDL particle size. Pre beta HDL particles were formed effectively in the absence of apoM expression; however, increased apoM expression stimulated the formation of larger-sized nascent pre beta HDLs. Immunoprecipitation with anti-apoA-I antibody followed by apoM Western blot analysis revealed that little secreted apoM was physically associated with pre beta HDL. Our results suggest that apoM is an atypical secretory protein that is not necessary for ABCA1-dependent pre beta HDL formation but does stimulate the formation of larger-sized pre beta HDL. We propose that apoM may function catalytically at an intracellular site to transfer lipid onto pre beta HDL during or after their formation by ABCA1. |
| File Format | HTM / HTML |
| ISSN | 00222275 |
| e-ISSN | 15397262 |
| DOI | 10.1194/jlr.M002162 |
| Journal | The Journal of Lipid Research |
| Issue Number | 3 |
| Volume Number | 51 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology |
| Publisher Date | 2010-03-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Discipline Biochemistry Atp-binding Cassette Transporters Metabolism Apolipoproteins Gene Expression Regulation High-density Lipoproteins, Pre-beta Chemistry Particle Size Atp Binding Cassette Transporter 1 Amino Acid Sequence Animals Genetics Isolation & Purification Carbonates Cell Line Cloning, Molecular Dna, Complementary Intracellular Space Lipocalins Molecular Sequence Data Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Endocrinology |
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