Differential expression of ACAT1 and ACAT2 among cells within liver, intestine, kidney, and adrenal of nonhuman primates
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2000-12-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520323609 |
| _version_ | 1818936741307875328 |
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| author | Richard G. Lee Mark C. Willingham Matthew A. Davis Kelly A. Skinner Lawrence L. Rudel |
| author_facet | Richard G. Lee Mark C. Willingham Matthew A. Davis Kelly A. Skinner Lawrence L. Rudel |
| author_sort | Richard G. Lee |
| collection | DOAJ |
| description | 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. |
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| issn | 0022-2275 |
| language | English |
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| publishDate | 2000-12-01 |
| publisher | Elsevier |
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| series | Journal of Lipid Research |
| spelling | doaj.art-df3ebc1505c44f0aada80dcc8e6dae7c2022-12-21T19:51:28ZengElsevierJournal of Lipid Research0022-22752000-12-01411219912001Differential expression of ACAT1 and ACAT2 among cells within liver, intestine, kidney, and adrenal of nonhuman primatesRichard G. Lee0Mark C. Willingham1Matthew A. Davis2Kelly A. Skinner3Lawrence L. Rudel4Arteriosclerosis Research Program, Departments of Pathology and Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157Arteriosclerosis Research Program, Departments of Pathology and Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157Arteriosclerosis Research Program, Departments of Pathology and Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157Arteriosclerosis Research Program, Departments of Pathology and Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157To whom correspondence should be addressed.; Arteriosclerosis Research Program, Departments of Pathology and Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157Two 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.http://www.sciencedirect.com/science/article/pii/S0022227520323609cholesterolenterocyteshepatocytesimmunolocalizationlipoproteins |
| spellingShingle | Richard G. Lee Mark C. Willingham Matthew A. Davis Kelly A. Skinner Lawrence L. Rudel Differential expression of ACAT1 and ACAT2 among cells within liver, intestine, kidney, and adrenal of nonhuman primates Journal of Lipid Research cholesterol enterocytes hepatocytes immunolocalization lipoproteins |
| title | Differential expression of ACAT1 and ACAT2 among cells within liver, intestine, kidney, and adrenal of nonhuman primates |
| title_full | Differential expression of ACAT1 and ACAT2 among cells within liver, intestine, kidney, and adrenal of nonhuman primates |
| title_fullStr | Differential expression of ACAT1 and ACAT2 among cells within liver, intestine, kidney, and adrenal of nonhuman primates |
| title_full_unstemmed | Differential expression of ACAT1 and ACAT2 among cells within liver, intestine, kidney, and adrenal of nonhuman primates |
| title_short | Differential expression of ACAT1 and ACAT2 among cells within liver, intestine, kidney, and adrenal of nonhuman primates |
| title_sort | differential expression of acat1 and acat2 among cells within liver intestine kidney and adrenal of nonhuman primates |
| topic | cholesterol enterocytes hepatocytes immunolocalization lipoproteins |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520323609 |
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