Intestinal cells assemble chylomicrons to transport dietary fat and fat-soluble vitamins. We have developed a cell culture model to study the assembly and secretion of these lipoproteins. The assembly of lipoproteins is critically dependent on two proteins, apolipoprotein B (apoB) and microsomal triglyceride transfer protein (MTP). It is known that physical interactions between apoB and MTP are important for lipoprotein assembly. We are in the process of identifying the binding sites involved in these protein-protein interactions in order to understand their physiologic role. Our goal is to understand the role of cell-surface receptors, intracellular chaperones, other apolipoproteins, and lipid transfer proteins in the biosynthesis of chylomicrons and the incorporation of fat-soluble vitamins into these lipoproteins. In addition, we would like to understand the mode of action of inhibitors that specifically inhibit chylomicron assembly and secretion, and evaluate their therapeutic potentials in the lowering of plasma cholesterol and triglyceride levels. Funded by multiple grants from the National Institute of Health and the American Heart Association.
RECENT PUBLICATIONS
1. Luchoomun, J., Zhou, Z., Bakillah, A., Jamil, H., and Hussain, M. M. Assembly and secretion of VLDL in nondifferentiated Caco-2 cells stably transfected with human recombinant apo B48 cDNA. Arterioscl. Thromb. Vasc. Biol. 17:2955-2963. 1997.
2. Hussain, M. M., Bakillah, A., and Jamil, H. Apolipoprotein B binding to microsomal triglyceride transfer protein decreases with increases in length and lipidation: implications in lipoprotein biosynthesis. Biochemistry. 36:13060-13067. 1997
3. Bakillah, A., Jamil, H., and Hussain, M.M. Lysine and arginine residues in the N-terminal 18% of apoliporotein B are critical for its binding to microsomal triglyceride transfer protein. Biochemistry. 37:3727-3734. 1998.
4. Hussain, M.M., Bakillah, A., Nayak, N., and Shelness, G.S. Amino acids 430-570 in apolipoprotein B are critical for its binding to microsomal triglyceride transfer protein. J. Biol. Chem. 273:25612-25615. 1998.
5. Luchoomun, J., and Hussain, M.M. Assembly and secretion of chylomicrons by differentiated Caco-2 cells: nascent triglycerides and preformed phospholipids are preferentially used for lipoprotein assembly.J. Biol. Chem. 274:19565-19572. 1999
6. Hussain, M.M. A proposed model for the assembly of chylomicrons. Atherosclerosis 148:1-15. 2000.
M. MAHMOOD HUSSAIN, Ph.D.
Associate Professor
Department of Anatomy and Cell Biology, Box #: 5
Phone: 270-4790 Fax: 270-3732
e-mail: mmahmoodhussain@downstate.edu
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