Sterol carrier protein-2 overexpression enhances sterol cycling and inhibits cholesterol ester synthesis and high density lipoprotein cholesterol secretion
| Autor: | Margaret E. Groh, Kevin Schadick, Erica J. Reschly, Apurba K. Gayen, Charles Baum |
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| Rok vydání: | 1997 |
| Předmět: |
Squalene
Very low-density lipoprotein Sterol O-acyltransferase Cholesterol 7 alpha-hydroxylase Transfection Biochemistry chemistry.chemical_compound Apolipoproteins E Liver Neoplasms Experimental Desmosterol Tumor Cells Cultured Animals Molecular Biology Plant Proteins biology Apolipoprotein A-I Cholesterol Reverse cholesterol transport Cell Membrane Cholesterol HDL Cell Biology Sterol Hydroxycholesterols Rats Sterols chemistry Liver HMG-CoA reductase biology.protein lipids (amino acids peptides and proteins) Cholesterol Esters Carrier Proteins |
| Zdroj: | The Journal of biological chemistry. 272(10) |
| ISSN: | 0021-9258 |
| Popis: | Recent data indicate that sterol carrier protein-2 (SCP-2) functions in the rapid movement of newly synthesized cholesterol to the plasma membrane (Puglielli, L., Rigotti, A., Greco, A. V., Santos, M. J., and Nervi, F. (1995) J. Biol. Chem. 270, 18723-18726). In order to further characterize the cellular function of SCP-2, we transfected McA-RH7777 rat hepatoma cells with a pre-SCP-2 cDNA expression construct. In stable transfectants, pre-SCP-2 processing resulted in an 8-fold increase in peroxisomal levels of SCP-2. SCP-2 overexpression increased the rates of newly synthesized cholesterol transfer to the plasma membrane and plasma membrane cholesterol internalization by 4-fold. There was no effect of SCP-2 overexpression on the microsomal levels of acyl-CoA:cholesterol acyltransferase and neutral cholesterol ester (CE) hydrolase; however, in the intact cell, CE synthesis and mass were reduced by 50%. SCP-2 overexpression also reduced high density lipoprotein-cholesterol secretion and apoA-I gene expression by 70% and doubled the rate of plasma membrane desmosterol conversion to cholesterol. We conclude that SCP-2 overexpression enhances the rate of cholesterol cycling, which reduces the availability of cholesterol for CE synthesis and alters the activity of a cellular cholesterol pool involved in regulating apoA-I-mediated high density lipoprotein cholesterol secretion. The net result of these changes in cholesterol metabolism is a 46% increase in plasma membrane cholesterol content, the implications of which are discussed. |
| Databáze: | OpenAIRE |
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