Perilipin 2 (PLIN2)-deficiency does not increase cholesterol-induced toxicity in macrophages.
Interventions on macrophages/foam cells to redirect intracellular cholesterol towards efflux pathways could become a very valuable addition to our therapeutic arsenal against atherosclerosis. However, certain manipulations of the cholesteryl ester cycle, such as the inhibition of ACAT1, an ER-reside...
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0033063&type=printable |
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| author | Se-Hee Son Young-Hwa Goo Benny H Chang Antoni Paul |
| author_facet | Se-Hee Son Young-Hwa Goo Benny H Chang Antoni Paul |
| author_sort | Se-Hee Son |
| collection | DOAJ |
| description | Interventions on macrophages/foam cells to redirect intracellular cholesterol towards efflux pathways could become a very valuable addition to our therapeutic arsenal against atherosclerosis. However, certain manipulations of the cholesteryl ester cycle, such as the inhibition of ACAT1, an ER-resident enzyme that re-esterifies cholesterol, are not well tolerated. Previously we showed that targeting perilipin-2 (PLIN2), a major lipid droplet (LD)-associated protein in macrophages, prevents foam cell formation and protects against atherosclerosis. Here we have assessed the tolerance of PLIN2-deficient bone marrow derived macrophages (BMM) to several lipid loading conditions similar to the found during atherosclerosis development, including exposure to modified low-density lipoprotein (mLDL) and 7-ketocholesterol (7-KC), a free cholesterol (FC) metabolite, in media with or without cholesterol acceptors. BMM isolated from mice that do or do not express PLIN2 were tested for apoptosis (TUNEL and cleaved caspase-3), ER stress (CHOP induction and XBP-1 splicing), and inflammation (TNF-α and IL-6 mRNA levels). Like in other cell types, PLIN2 deficiency impairs LD buildup in BMM. However, while most stress parameters were elevated in macrophages under ACAT inhibition and 7-KC loading, PLIN2 inactivation was well tolerated. The data support the safety of targeting PLIN2 to prevent foam cell formation and atherosclerosis. |
| format | Article |
| id | doaj-art-fc05797f2e2e4e8a90d338ff38ca81cc |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj-art-fc05797f2e2e4e8a90d338ff38ca81cc2025-08-20T02:30:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0173e3306310.1371/journal.pone.0033063Perilipin 2 (PLIN2)-deficiency does not increase cholesterol-induced toxicity in macrophages.Se-Hee SonYoung-Hwa GooBenny H ChangAntoni PaulInterventions on macrophages/foam cells to redirect intracellular cholesterol towards efflux pathways could become a very valuable addition to our therapeutic arsenal against atherosclerosis. However, certain manipulations of the cholesteryl ester cycle, such as the inhibition of ACAT1, an ER-resident enzyme that re-esterifies cholesterol, are not well tolerated. Previously we showed that targeting perilipin-2 (PLIN2), a major lipid droplet (LD)-associated protein in macrophages, prevents foam cell formation and protects against atherosclerosis. Here we have assessed the tolerance of PLIN2-deficient bone marrow derived macrophages (BMM) to several lipid loading conditions similar to the found during atherosclerosis development, including exposure to modified low-density lipoprotein (mLDL) and 7-ketocholesterol (7-KC), a free cholesterol (FC) metabolite, in media with or without cholesterol acceptors. BMM isolated from mice that do or do not express PLIN2 were tested for apoptosis (TUNEL and cleaved caspase-3), ER stress (CHOP induction and XBP-1 splicing), and inflammation (TNF-α and IL-6 mRNA levels). Like in other cell types, PLIN2 deficiency impairs LD buildup in BMM. However, while most stress parameters were elevated in macrophages under ACAT inhibition and 7-KC loading, PLIN2 inactivation was well tolerated. The data support the safety of targeting PLIN2 to prevent foam cell formation and atherosclerosis.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0033063&type=printable |
| spellingShingle | Se-Hee Son Young-Hwa Goo Benny H Chang Antoni Paul Perilipin 2 (PLIN2)-deficiency does not increase cholesterol-induced toxicity in macrophages. PLoS ONE |
| title | Perilipin 2 (PLIN2)-deficiency does not increase cholesterol-induced toxicity in macrophages. |
| title_full | Perilipin 2 (PLIN2)-deficiency does not increase cholesterol-induced toxicity in macrophages. |
| title_fullStr | Perilipin 2 (PLIN2)-deficiency does not increase cholesterol-induced toxicity in macrophages. |
| title_full_unstemmed | Perilipin 2 (PLIN2)-deficiency does not increase cholesterol-induced toxicity in macrophages. |
| title_short | Perilipin 2 (PLIN2)-deficiency does not increase cholesterol-induced toxicity in macrophages. |
| title_sort | perilipin 2 plin2 deficiency does not increase cholesterol induced toxicity in macrophages |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0033063&type=printable |
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