Synthesis and secretion of apoE in thioglycolate-elicited mouse peritoneal macrophages: effect of cholesterol efflux.
ApoE synthesis and secretion, as a function of cellular cholesterol content and cholesterol efflux, was studied in thioglycolate-elicited mouse peritoneal macrophages. As expected, loading elicited macrophages with cholesterol induced a 5-fold increase in apoE secretion and a 2.5-fold increase in ce...
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| Format: | Article |
| Language: | English |
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Elsevier
1989-06-01
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| Series: | Journal of Lipid Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520383036 |
| _version_ | 1819291107963437056 |
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| author | L Dory |
| author_facet | L Dory |
| author_sort | L Dory |
| collection | DOAJ |
| description | ApoE synthesis and secretion, as a function of cellular cholesterol content and cholesterol efflux, was studied in thioglycolate-elicited mouse peritoneal macrophages. As expected, loading elicited macrophages with cholesterol induced a 5-fold increase in apoE secretion and a 2.5-fold increase in cellular apoE content over a 5-h period. Treatment of cholesterol-loaded cells with HDL3 further increased apoE secretion 1.7-fold and decreased cellular cholesterol by 20%. Treatment of cholesterol-loaded cells with HDL3 and SAH 58.035 (an ACAT inhibitor) increased apoE secretion 2.4-fold and decreased cellular cholesterol content by 35%. Treatment of the cells with the ACAT inhibitor alone suppressed apoE secretion by 40% but did not change cellular cholesterol content. Northern blot analysis of RNA indicated that cholesterol loading increased apoE mRNA 2-fold. ApoE mRNA levels were not further affected by treatment with HDL3 and/or the ACAT inhibitor. Cholesterol-loaded cells, in the absence of HDL3, secreted apoE into the media in two fractions as determined by column chromatography: a large molecular weight complex, (larger than HDL), and an essentially lipid-free protein. In the presence of HDL3, the cells secreted apoE in three fractions: a large molecular weight complex, an essentially lipid-free protein, and over 50% of apoE associated with HDL. In the process, HDL3 became larger and eluted in a position identical to that of HDL2. A small amount of HDL3-derived material was also transformed to an LDL-size particle. Incubation of HDL3 in the absence of cholesterol-loaded cells did not produce these changes. It is concluded that cholesterol-loading increases apoE mRNA content and apoE synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) |
| first_indexed | 2024-12-24T03:33:23Z |
| format | Article |
| id | doaj.art-740d0ab04cc541deb0fea3f1cdf47f0d |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-24T03:33:23Z |
| publishDate | 1989-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-740d0ab04cc541deb0fea3f1cdf47f0d2022-12-21T17:17:07ZengElsevierJournal of Lipid Research0022-22751989-06-01306809816Synthesis and secretion of apoE in thioglycolate-elicited mouse peritoneal macrophages: effect of cholesterol efflux.L Dory0Department of Pharmacology, College of Medicine, University of Tennessee, Memphis 38163.ApoE synthesis and secretion, as a function of cellular cholesterol content and cholesterol efflux, was studied in thioglycolate-elicited mouse peritoneal macrophages. As expected, loading elicited macrophages with cholesterol induced a 5-fold increase in apoE secretion and a 2.5-fold increase in cellular apoE content over a 5-h period. Treatment of cholesterol-loaded cells with HDL3 further increased apoE secretion 1.7-fold and decreased cellular cholesterol by 20%. Treatment of cholesterol-loaded cells with HDL3 and SAH 58.035 (an ACAT inhibitor) increased apoE secretion 2.4-fold and decreased cellular cholesterol content by 35%. Treatment of the cells with the ACAT inhibitor alone suppressed apoE secretion by 40% but did not change cellular cholesterol content. Northern blot analysis of RNA indicated that cholesterol loading increased apoE mRNA 2-fold. ApoE mRNA levels were not further affected by treatment with HDL3 and/or the ACAT inhibitor. Cholesterol-loaded cells, in the absence of HDL3, secreted apoE into the media in two fractions as determined by column chromatography: a large molecular weight complex, (larger than HDL), and an essentially lipid-free protein. In the presence of HDL3, the cells secreted apoE in three fractions: a large molecular weight complex, an essentially lipid-free protein, and over 50% of apoE associated with HDL. In the process, HDL3 became larger and eluted in a position identical to that of HDL2. A small amount of HDL3-derived material was also transformed to an LDL-size particle. Incubation of HDL3 in the absence of cholesterol-loaded cells did not produce these changes. It is concluded that cholesterol-loading increases apoE mRNA content and apoE synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)http://www.sciencedirect.com/science/article/pii/S0022227520383036 |
| spellingShingle | L Dory Synthesis and secretion of apoE in thioglycolate-elicited mouse peritoneal macrophages: effect of cholesterol efflux. Journal of Lipid Research |
| title | Synthesis and secretion of apoE in thioglycolate-elicited mouse peritoneal macrophages: effect of cholesterol efflux. |
| title_full | Synthesis and secretion of apoE in thioglycolate-elicited mouse peritoneal macrophages: effect of cholesterol efflux. |
| title_fullStr | Synthesis and secretion of apoE in thioglycolate-elicited mouse peritoneal macrophages: effect of cholesterol efflux. |
| title_full_unstemmed | Synthesis and secretion of apoE in thioglycolate-elicited mouse peritoneal macrophages: effect of cholesterol efflux. |
| title_short | Synthesis and secretion of apoE in thioglycolate-elicited mouse peritoneal macrophages: effect of cholesterol efflux. |
| title_sort | synthesis and secretion of apoe in thioglycolate elicited mouse peritoneal macrophages effect of cholesterol efflux |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520383036 |
| work_keys_str_mv | AT ldory synthesisandsecretionofapoeinthioglycolateelicitedmouseperitonealmacrophageseffectofcholesterolefflux |