ACAT2 is localized to Hepatocytes and is the major cholesterol-esterifying enzyme in human liver

被引:185
作者
Parini, P
Davis, M
Lada, AT
Erickson, SK
Wright, TL
Gustafsson, U
Sahlin, S
Einarsson, C
Eriksson, M
Angelin, B
Tomoda, H
Omura, S
Willingham, MC
Rudel, LL
机构
[1] Wake Forest Univ, Bowman Gray Sch Med, Dept Pathol, Winston Salem, NC 27157 USA
[2] Huddinge Univ Hosp, Karolinska Inst, Novum,Dept Med,Metab Unit, Ctr Metab & Endocrinol, S-14186 Huddinge, Sweden
[3] Huddinge Univ Hosp, Karolinska Inst, Ctr Nutr & Toxicol, Mol Nutr Unit, S-14186 Huddinge, Sweden
[4] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
[5] Univ Calif San Francisco, Ctr Liver, San Francisco, CA 94143 USA
[6] Vet Adm Med Ctr, San Francisco, CA 94121 USA
[7] Danderyd Hosp, Dept Surg, Karolinska Inst, S-18288 Danderyd, Sweden
[8] Huddinge Univ Hosp, Karolinska Inst, Dept Med, Ctr Gastroenterol, S-14186 Huddinge, Sweden
[9] Kitasato Univ, Kitasato Inst Life Sci, Tokyo, Japan
[10] Wake Forest Univ, Bowman Gray Sch Med, Dept Biochem, Winston Salem, NC 27103 USA
关键词
cholesterol; genes; lipids; metabolism;
D O I
10.1161/01.CIR.0000143163.76212.0B
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background-Two acyl-coenzyme A: cholesterol acyltransferase ( ACAT) genes, ACAT1 and ACAT2, have been identified that encode 2 proteins responsible for intracellular cholesterol esterification. Methods and Results-In this study, immunohistology was used to establish their cellular localization in human liver biopsies. ACAT2 protein expression was confined to hepatocytes, whereas ACAT1 protein was found in Kupffer cells only. Studies with a highly specific ACAT2 inhibitor, pyripyropene A, in microsomal activity assays demonstrated that ACAT2 activity was highly variable among individual human liver samples, whereas ACAT1 activity was more similar in all specimens. ACAT2 provided the major cholesterol-esterifying activity in 3 of 4 human liver samples examined. Conclusions-The data suggest that in diseases in which dysregulation of cholesterol metabolism occurs, such as hypercholesterolemia and atherosclerosis, ACAT2 should be considered a target for prevention and treatment.
引用
收藏
页码:2017 / 2023
页数:7
相关论文
共 31 条
  • [1] Massive xanthomatosis and altered composition of atherosclerotic lesions in hyperlipidemic mice lacking acyl CoA:cholesterol acyltransferase 1
    Accad, M
    Smith, SJ
    Newland, DL
    Sanan, DA
    King, LE
    Linton, MF
    Fazio, S
    Farese, RV
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2000, 105 (06) : 711 - 719
  • [2] Identification of a form of acyl-CoA:cholesterol acyltransferase specific to liver and intestine in nonhuman primates
    Anderson, RA
    Joyce, C
    Davis, M
    Reagan, JW
    Clark, M
    Shelness, GS
    Rudel, LL
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (41) : 26747 - 26754
  • [3] Resistance to diet-induced hypercholesterolemia and gallstone formation in ACAT2-deficient mice
    Buhman, KK
    Accad, M
    Novak, S
    Choi, RS
    Wong, JS
    Hamilton, RL
    Turley, S
    Farese, RV
    [J]. NATURE MEDICINE, 2000, 6 (12) : 1341 - 1347
  • [4] The enzymes of neutral lipid synthesis
    Buhman, KK
    Chen, HC
    Farese, RV
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (44) : 40369 - 40372
  • [5] HEPATIC ACAT ACTIVITY IN AFRICAN-GREEN MONKEYS IS HIGHLY CORRELATED TO PLASMA LDL CHOLESTERYL ESTER ENRICHMENT AND CORONARY-ARTERY ATHEROSCLEROSIS
    CARR, TP
    PARKS, JS
    RUDEL, LL
    [J]. ARTERIOSCLEROSIS AND THROMBOSIS, 1992, 12 (11): : 1274 - 1283
  • [6] ACAT-2, a second mammalian acyl-CoA:cholesterol acyltransferase -: Its cloning, expression, and characterization
    Cases, S
    Novak, S
    Zheng, YW
    Myers, HM
    Lear, SR
    Sande, E
    Welch', CB
    Lusis, AJ
    Spencer, TA
    Krause, BR
    Erickson, SK
    Farese, RV
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (41) : 26755 - 26764
  • [7] Chang CCY, 2000, J BIOL CHEM, V275, P28083
  • [8] Roles of acyl-coenzyme A:cholesterol acyltransferase-1 and-2
    Chang, TY
    Chang, CCY
    Lin, S
    Yu, CJ
    Li, BL
    Miyazaki, A
    [J]. CURRENT OPINION IN LIPIDOLOGY, 2001, 12 (03) : 289 - 296
  • [9] EINARSSON K, 1989, J LIPID RES, V30, P739
  • [10] ACYL-COENZYME-A - CHOLESTEROL ACYLTRANSFERASE IN HUMAN-LIVER - INVITRO DETECTION AND SOME CHARACTERISTICS OF THE ENZYME
    ERICKSON, SK
    COOPER, AD
    [J]. METABOLISM-CLINICAL AND EXPERIMENTAL, 1980, 29 (10): : 991 - 996