| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Correspondence to:
Lawrence L. Rudel
Two closely related enzymes with more than 50% sequence identity have been identified that catalyze the esterification of cholesterol using acyl-CoA substrates, namely acyl-CoA:cholesterol acyltransferase 1 (ACAT1) and ACAT2. Both are membrane-spanning proteins believed to reside in the endoplasmic reticulum of cells. ACAT2 has been hypothesized to be associated with lipoprotein particle secretion whereas ACAT1 is ubiquitous and may serve a more general role in cellular cholesterol homeostasis. We have prepared and affinity purified rabbit polyclonal antibodies unique to either ACAT enzyme to identify their cellular localization in liver and intestine, the two main lipoprotein-secreting tissues of the body, and for comparison, kidney and adrenal. In the liver, ACAT2 was identified in the rough endoplasmic reticulum of essentially all hepatocytes whereas ACAT1 was confined to cells lining the intercellular spaces among hepatocytes in a pattern typical of Kupffer cells. In the intestine, ACAT2 signal was strongly present in the apical third of the mucosal cells, whereas ACAT1 staining was diffuse throughout the mucosal cell, but with strong signal in goblet cells, Paneth cells, and villus macrophages. In the kidney, ACAT1 immunostaining was specific for the distal tubules and podocytes within the glomerulus. In the adrenal, ACAT1 signal was strongly present in the cells of the cortex, and absent from other adrenal cell types. No ACAT2 signal was identified in the kidney or adrenal.
We conclude that only the cells of the liver and intestine that secrete apolipoprotein B-containing lipoproteins contain ACAT2, whereas ACAT1 is present in numerous other cell types. The data clearly suggest separate functions for these two closely related enzymes, with ACAT2 being most closely associated with plasma cholesterol levels. — Lee, R. G., M. C. Willingham, M. A. Davis, K. A. Skinner, and L. L. Rudel. Differential expression of ACAT1 and ACAT2 among cells within liver, intestine, kidney, and adrenal of nonhuman primates. J. Lipid Res. 2000. 41: 1991;–2001.
Supplementary key words:
cholesterol, enterocytes, hepatocytes, immunolocalization, lipoproteins
Copyright © 2000 by Lipid Research, Inc.
Original Article
Differential expression of ACAT1 and ACAT2 among cells within liver, intestine, kidney, and adrenal of nonhuman primates
Richard G. Leea,
Mark C. Willinghama,
Matthew A. Davisa,
Kelly A. Skinnera, and
Lawrence L. Rudela
a Arteriosclerosis Research Program, Departments of Pathology and Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Das, M. A. Davis, and L. L. Rudel Identification of putative active site residues of ACAT enzymes J. Lipid Res., August 1, 2008; 49(8): 1770 - 1781. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Iqbal, L. L. Rudel, and M. M. Hussain Microsomal Triglyceride Transfer Protein Enhances Cellular Cholesteryl Esterification by Relieving Product Inhibition J. Biol. Chem., July 18, 2008; 283(29): 19967 - 19980. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Myhill, E. M. Lynes, J. A. Nanji, A. D. Blagoveshchenskaya, H. Fei, K. Carmine Simmen, T. J. Cooper, G. Thomas, and T. Simmen The Subcellular Distribution of Calnexin Is Mediated by PACS-2 Mol. Biol. Cell, July 1, 2008; 19(7): 2777 - 2788. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Brown, T. A. Bell III, H. M. Alger, J. K. Sawyer, T. L. Smith, K. Kelley, R. Shah, M. D. Wilson, M. A. Davis, R. G. Lee, et al. Targeted Depletion of Hepatic ACAT2-driven Cholesterol Esterification Reveals a Non-biliary Route for Fecal Neutral Sterol Loss J. Biol. Chem., April 18, 2008; 283(16): 10522 - 10534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Das, M. A. Davis, H. Tomoda, S. Omura, and L. L. Rudel Identification of the Interaction Site within Acyl-CoA:Cholesterol Acyltransferase 2 for the Isoform-specific Inhibitor Pyripyropene A J. Biol. Chem., April 18, 2008; 283(16): 10453 - 10460. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. E. Temel, L. Hou, L. L. Rudel, and G. S. Shelness ACAT2 stimulates cholesteryl ester secretion in apoB-containing lipoproteins J. Lipid Res., July 1, 2007; 48(7): 1618 - 1627. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Spector and W. G. Haynes LDL Cholesteryl Oleate: A Biomarker for Atherosclerosis? Arterioscler. Thromb. Vasc. Biol., June 1, 2007; 27(6): 1228 - 1230. [Full Text] [PDF]
|
|
|
|
|
|
T. A. Bell III, K. Kelley, M. D. Wilson, J. K. Sawyer, and L. L. Rudel Dietary Fat-Induced Alterations in Atherosclerosis Are Abolished by ACAT2-Deficiency in ApoB100 Only, LDLr-/- Mice Arterioscler. Thromb. Vasc. Biol., June 1, 2007; 27(6): 1396 - 1402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Bell III, J. M. Brown, M. J. Graham, K. M. Lemonidis, R. M. Crooke, and L. L. Rudel Liver-Specific Inhibition of Acyl-Coenzyme A:Cholesterol Acyltransferase 2 With Antisense Oligonucleotides Limits Atherosclerosis Development in Apolipoprotein B100-Only Low-Density Lipoprotein Receptor-/- Mice Arterioscler. Thromb. Vasc. Biol., August 1, 2006; 26(8): 1814 - 1820. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Nissen, E. M. Tuzcu, H. B. Brewer, I. Sipahi, S. J. Nicholls, P. Ganz, P. Schoenhagen, D. D. Waters, C. J. Pepine, T. D. Crowe, et al. Effect of ACAT inhibition on the progression of coronary atherosclerosis. N. Engl. J. Med., March 23, 2006; 354(12): 1253 - 1263. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. E. Temel, R. G. Lee, K. L. Kelley, M. A. Davis, R. Shah, J. K. Sawyer, M. D. Wilson, and L. L. Rudel Intestinal cholesterol absorption is substantially reduced in mice deficient in both ABCA1 and ACAT2 J. Lipid Res., November 1, 2005; 46(11): 2423 - 2431. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. L. Rudel, R. G. Lee, and P. Parini ACAT2 Is a Target for Treatment of Coronary Heart Disease Associated With Hypercholesterolemia Arterioscler. Thromb. Vasc. Biol., June 1, 2005; 25(6): 1112 - 1118. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. G. Lee, K. L. Kelley, J. K. Sawyer, R. V. Farese Jr, J. S. Parks, and L. L. Rudel Plasma Cholesteryl Esters Provided by Lecithin:Cholesterol Acyltransferase and Acyl-Coenzyme A:Cholesterol Acyltransferase 2 Have Opposite Atherosclerotic Potential Circ. Res., November 12, 2004; 95(10): 998 - 1004. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Parini, M. Davis, A. T. Lada, S. K. Erickson, T. L. Wright, U. Gustafsson, S. Sahlin, C. Einarsson, M. Eriksson, B. Angelin, et al. ACAT2 Is Localized to Hepatocytes and Is the Major Cholesterol-Esterifying Enzyme in Human Liver Circulation, October 5, 2004; 110(14): 2017 - 2023. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Smith, K. Rangaraj, R. Simpson, D. J. Maclean, L. K. Nathanson, K. A. Stuart, S. P. Scott, G. A. Ramm, and J. de Jersey Quantitative analysis of the expression of ACAT genes in human tissues by real-time PCR2 J. Lipid Res., April 1, 2004; 45(4): 686 - 696. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. T. Lada, M. Davis, C. Kent, J. Chapman, H. Tomoda, S. Omura, and L. L. Rudel Identification of ACAT1- and ACAT2-specific inhibitors using a novel, cell-based fluorescence assay: individual ACAT uniqueness J. Lipid Res., February 1, 2004; 45(2): 378 - 386. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. E. Temel, A. K. Gebre, J. S. Parks, and L. L. Rudel Compared with Acyl-CoA:Cholesterol O-Acyltransferase (ACAT) 1 and Lecithin:Cholesterol Acyltransferase, ACAT2 Displays the Greatest Capacity to Differentiate Cholesterol from Sitosterol J. Biol. Chem., November 28, 2003; 278(48): 47594 - 47601. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ghosh, R. W. St. Clair, and L. L. Rudel Mobilization of cytoplasmic CE droplets by overexpression of human macrophage cholesteryl ester hydrolase J. Lipid Res., October 1, 2003; 44(10): 1833 - 1840. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Lin, X. Lu, C. C.Y. Chang, and T.-Y. Chang Human Acyl-Coenzyme A:Cholesterol Acyltransferase Expressed in Chinese Hamster Ovary Cells: Membrane Topology and Active Site Location Mol. Biol. Cell, June 1, 2003; 14(6): 2447 - 2460. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Botham, X. Zheng, M. Napolitano, M. Avella, C. Cavallari, R. Rivabene, and E. Bravo The Effects of Dietary n-3 Polyunsaturated Fatty Acids Delivered in Chylomicron Remnants on the Transcription of Genes Regulating Synthesis and Secretion of Very-Low-Density Lipoprotein by the Liver: Modulation by Cellular Oxidative State Experimental Biology and Medicine, February 1, 2003; 228(2): 143 - 151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Chao, M. Zhou, A. McIntosh, F. Schroeder, and A. B. Kier ACBP and cholesterol differentially alter fatty acyl CoA utilization by microsomal ACAT J. Lipid Res., January 1, 2003; 44(1): 72 - 83. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. L. Rudel, M. Davis, J. Sawyer, R. Shah, and J. Wallace Primates Highly Responsive to Dietary Cholesterol Up-regulate Hepatic ACAT2, and Less Responsive Primates Do Not J. Biol. Chem., August 23, 2002; 277(35): 31401 - 31406. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Y. Chang, C. C. Y. Chang, X. Lu, and S. Lin Catalysis of ACAT may be completed within the plane of the membrane: a working hypothesis J. Lipid Res., December 1, 2001; 42(12): 1933 - 1938. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Fusegawa, K. L. Kelley, J. K. Sawyer, R. N. Shah, and L. L. Rudel Influence of dietary fatty acid composition on the relationship between CETP activity and plasma lipoproteins in monkeys J. Lipid Res., November 1, 2001; 42(11): 1849 - 1857. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Merkel, W. Velez-Carrasco, L. C. Hudgins, and J. L. Breslow Compared with saturated fatty acids, dietary monounsaturated fatty acids and carbohydrates increase atherosclerosis and VLDL cholesterol levels in LDL receptor-deficient, but not apolipoprotein E-deficient, mice PNAS, October 16, 2001; (2001) 231490498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. J. Wilcox, N. M. Borradaile, L. E. de Dreu, and M. W. Huff Secretion of hepatocyte apoB is inhibited by the flavonoids, naringenin and hesperetin, via reduced activity and expression of ACAT2 and MTP J. Lipid Res., May 1, 2001; 42(5): 725 - 734. [Abstract] [Full Text]
|
|
|
|
|
|
J.-B. Yang, Z.-J. Duan, W. Yao, O. Lee, L. Yang, X.-Y. Yang, X. Sun, C. C. Y. Chang, T.-Y. Chang, and B.-L. Li Synergistic Transcriptional Activation of Human Acyl-coenzyme A: Cholesterol Acyltransterase-1 Gene by Interferon-gamma and All-trans-Retinoic Acid THP-1 Cells J. Biol. Chem., June 8, 2001; 276(24): 20989 - 20998. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. K. Buhman, H. C. Chen, and R. V. Farese Jr. The Enzymes of Neutral Lipid Synthesis J. Biol. Chem., October 26, 2001; 276(44): 40369 - 40372. [Full Text] [PDF]
|
|
|
|
|
|
M. Merkel, W. Velez-Carrasco, L. C. Hudgins, and J. L. Breslow Compared with saturated fatty acids, dietary monounsaturated fatty acids and carbohydrates increase atherosclerosis and VLDL cholesterol levels in LDL receptor-deficient, but not apolipoprotein E-deficient, mice PNAS, November 6, 2001; 98(23): 13294 - 13299. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Journal of Biological Chemistry |
| Molecular and Cellular Proteomics | ASBMB Today |
