An inhibitor of the microsomal triglyceride transfer protein inhibits apoB secretion from HepG2 cells
| Autor: | Carl P. Ciosek, John R. Wetterau, Richard E. Gregg, Ying Chen, Scott A. Biller, Ching-Hsuen Chu, Thomas Harrity, Jamil Haris, David C. Eustice, Beverly Ricci, David A. Gordon, Cindy M. Brooks, John K. Dickson |
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| Rok vydání: | 1996 |
| Předmět: |
Carcinoma
Hepatocellular Indoles Apolipoprotein B Isoindoles Tritium Microsomal triglyceride transfer protein Cell Line chemistry.chemical_compound Piperidines Microsomes Cholesterylester transfer protein medicine Tumor Cells Cultured Animals Humans Triglycerides Apolipoproteins B Glycoproteins Multidisciplinary biology Chemistry Liver Neoplasms Abetalipoproteinemia medicine.disease Cholesterol Ester Transfer Proteins Kinetics Biochemistry biology.protein Cholesteryl ester lipids (amino acids peptides and proteins) Cattle Carrier Proteins Plant lipid transfer proteins Lipoprotein Chylomicron Protein Binding Research Article |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 93(21) |
| ISSN: | 0027-8424 |
| Popis: | The microsomal triglyceride (TG) transfer protein (MTP) is a heterodimeric lipid transfer protein that catalyzes the transport of triglyceride, cholesteryl ester, and phosphatidylcholine between membranes. Previous studies showing that the proximal cause of abetalipoproteinemia is an absence of MTP indicate that MTP function is required for the assembly of the apolipoprotein B (apoB) containing plasma lipoproteins, i.e., very low density lipoproteins and chylomicrons. However, the precise role of MTP in lipoprotein assembly is not known. In this study, the role of MTP in lipoprotein assembly is investigated using an inhibitor of MTP-mediated lipid transport, 2-[1-(3, 3-diphenylpropyl)-4-piperidinyl]-2,3-dihydro-1H-isoindol-1-o ne (BMS-200150). The similarity of the IC50 for inhibition of bovine MTP-mediated TG transfer (0.6 microM) to the Kd for binding of BMS-200150 to bovine MTP (1.3 microM) strongly supports that the inhibition of TG transfer is the result of a direct effect of the compound on MTP. BMS-200150 also inhibits the transfer of phosphatidylcholine, however to a lesser extent (30% at a concentration that almost completely inhibits TG and cholesteryl ester transfer). When BMS-200150 is added to cultured HepG2 cells, a human liver-derived cell line that secretes apoB containing lipoproteins, it inhibits apoB secretion in a concentration dependent manner. These results support the hypothesis that transport of lipid, and in particular, the transport of neutral lipid by MTP, plays a critical role in the assembly of apoB containing lipoproteins. |
| Databáze: | OpenAIRE |
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