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| ACAT-2, a second mammalian acyl-CoA : cholesterol acyltransferase - Its cloning, expression, and characterization |
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| Author(s): Cases S, Novak S, Zheng YW, Myers HM, Lear SR, Sande E, Welch' CB, Lusis AJ, Spencer TA, Krause BR, Erickson SK, Farese RV |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 273 Issue: 41 Pages: 26755-26764 Published: OCT 9 1998 |
| Times Cited: 184 References: 59 |
| Abstract: The synthesis of cholesterol esters by acyl-CoA:cholesterol acyltransferase (ACAT, EC 2.3.1.26) is an important component of cellular cholesterol homeostasis, Cholesterol ester formation also is hypothesized to be important in several physiologic processes, including intestinal cholesterol absorption, hepatic lipoprotein production, and macrophage foam cell formation in atherosclerotic lesions. Mouse tissue expression studies and the disruption of the mouse ACAT gene (Acact) have indicated that more than one ACAT exists in mammals and specifically that another enzyme is important in mouse liver and intestine. We now describe a second mammalian ACAT enzyme, designated ACAT-2, that is 44% identical to the first cloned mouse ACAT (henceforth designated ACAT-1), Infection of H5 insect cells with an ACAT-2 recombinant baculovirus resulted in expression of a similar to 46-kDa protein in cell membranes that was associated with high levels of cholesterol esterification activity. Both ACAT-1 and ACAT-2 also catalyzed the esterification of the SP-hydroxyl group of a variety of oxysterols, Cholesterol esterification activities for ACAT-1 and ACAT-2 exhibited different IC50 values when assayed in the presence of several ACAT-specific inhibitors, demonstrating that ACAT inhibitors can selectively target specific forms of ACAT, ACAT-2 was expressed primarily in mouse liver and small intestine, supporting the hypothesis that ACAT-2 contributes to cholesterol esterification in these tissues. The mouse ACAT-S gene (Acact2) maps to chromosome 15 in a region containing a quantitative trait locus influencing plasma cholesterol levels. The identification and cloning of ACAT-S will facilitate molecular approaches to understanding the role of ACAT enzymes in mammalian biology. |
| Document Type: Article |
| Language: English |
| Reprint Address: Farese, RV (reprint author), Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, POB 419100, San Francisco, CA 94141 USA |
Addresses:
1. Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94141 USA
2. Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94141 USA
3. Univ Calif San Francisco, Dept Med, San Francisco, CA 94141 USA
4. Vet Adm Med Ctr, San Francisco, CA 94121 USA
5. Univ Calif Los Angeles, Dept Microbiol & Mol Genet, Los Angeles, CA 90095 USA
6. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA
7. Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA
8. Dartmouth Coll, Dept Chem, Hanover, NH 03755 USA
9. Parke Davis Pharmaceut Res, Ann Arbor, MI 48105 USA |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: 127WJ |
| ISSN: 0021-9258 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |