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Pharmacologic Inhibition of Sphingomyelin Synthase (SMS) Activity Reduces Apolipoprotein-B Secretion from Hepatocytes and Attenuates Endotoxin-Mediated Macrophage Inflammation
Sphingomyelin synthase (SMS) plays an important role in plasma atherogenic lipoprotein metabolism, inflammation, and the development of atherosclerosis. To understand whether the impaired apoB secretion and inflammation response is a direct result from lack of SMS activity, in this study, we prepare...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102531/ https://www.ncbi.nlm.nih.gov/pubmed/25032960 http://dx.doi.org/10.1371/journal.pone.0102641 |
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author | Lou, Bin Dong, Jibin Li, Yali Ding, Tingbo Bi, Tingting Li, Yue Deng, Xiaodong Ye, Deyong Jiang, Xian-Cheng |
author_facet | Lou, Bin Dong, Jibin Li, Yali Ding, Tingbo Bi, Tingting Li, Yue Deng, Xiaodong Ye, Deyong Jiang, Xian-Cheng |
author_sort | Lou, Bin |
collection | PubMed |
description | Sphingomyelin synthase (SMS) plays an important role in plasma atherogenic lipoprotein metabolism, inflammation, and the development of atherosclerosis. To understand whether the impaired apoB secretion and inflammation response is a direct result from lack of SMS activity, in this study, we prepared a series of compounds that inhibit SMS activity. Further, we characterized Dy105, the most potent inhibitor. We found that Dy105 treatment significantly reduces SM levels in SM-rich microdomain on cell membranes. Moreover, we found that SMS inhibition reduces apoB secretion in a human hepatoma cell line and reduces the activation of NFκB and p38, a MAP kinase, in bone marrow derived macrophages. These studies provided further evidence that SMS activity regulates atherogenic lipoprotein metabolism and inflammatory responses. Pharmacologic inhibition of SMS may be a new therapy for atherosclerosis by reducing apoB secretion, and reducing inflammation. |
format | Online Article Text |
id | pubmed-4102531 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-41025312014-07-21 Pharmacologic Inhibition of Sphingomyelin Synthase (SMS) Activity Reduces Apolipoprotein-B Secretion from Hepatocytes and Attenuates Endotoxin-Mediated Macrophage Inflammation Lou, Bin Dong, Jibin Li, Yali Ding, Tingbo Bi, Tingting Li, Yue Deng, Xiaodong Ye, Deyong Jiang, Xian-Cheng PLoS One Research Article Sphingomyelin synthase (SMS) plays an important role in plasma atherogenic lipoprotein metabolism, inflammation, and the development of atherosclerosis. To understand whether the impaired apoB secretion and inflammation response is a direct result from lack of SMS activity, in this study, we prepared a series of compounds that inhibit SMS activity. Further, we characterized Dy105, the most potent inhibitor. We found that Dy105 treatment significantly reduces SM levels in SM-rich microdomain on cell membranes. Moreover, we found that SMS inhibition reduces apoB secretion in a human hepatoma cell line and reduces the activation of NFκB and p38, a MAP kinase, in bone marrow derived macrophages. These studies provided further evidence that SMS activity regulates atherogenic lipoprotein metabolism and inflammatory responses. Pharmacologic inhibition of SMS may be a new therapy for atherosclerosis by reducing apoB secretion, and reducing inflammation. Public Library of Science 2014-07-17 /pmc/articles/PMC4102531/ /pubmed/25032960 http://dx.doi.org/10.1371/journal.pone.0102641 Text en © 2014 Lou et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Lou, Bin Dong, Jibin Li, Yali Ding, Tingbo Bi, Tingting Li, Yue Deng, Xiaodong Ye, Deyong Jiang, Xian-Cheng Pharmacologic Inhibition of Sphingomyelin Synthase (SMS) Activity Reduces Apolipoprotein-B Secretion from Hepatocytes and Attenuates Endotoxin-Mediated Macrophage Inflammation |
title | Pharmacologic Inhibition of Sphingomyelin Synthase (SMS) Activity Reduces Apolipoprotein-B Secretion from Hepatocytes and Attenuates Endotoxin-Mediated Macrophage Inflammation |
title_full | Pharmacologic Inhibition of Sphingomyelin Synthase (SMS) Activity Reduces Apolipoprotein-B Secretion from Hepatocytes and Attenuates Endotoxin-Mediated Macrophage Inflammation |
title_fullStr | Pharmacologic Inhibition of Sphingomyelin Synthase (SMS) Activity Reduces Apolipoprotein-B Secretion from Hepatocytes and Attenuates Endotoxin-Mediated Macrophage Inflammation |
title_full_unstemmed | Pharmacologic Inhibition of Sphingomyelin Synthase (SMS) Activity Reduces Apolipoprotein-B Secretion from Hepatocytes and Attenuates Endotoxin-Mediated Macrophage Inflammation |
title_short | Pharmacologic Inhibition of Sphingomyelin Synthase (SMS) Activity Reduces Apolipoprotein-B Secretion from Hepatocytes and Attenuates Endotoxin-Mediated Macrophage Inflammation |
title_sort | pharmacologic inhibition of sphingomyelin synthase (sms) activity reduces apolipoprotein-b secretion from hepatocytes and attenuates endotoxin-mediated macrophage inflammation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102531/ https://www.ncbi.nlm.nih.gov/pubmed/25032960 http://dx.doi.org/10.1371/journal.pone.0102641 |
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