Autor: |
Bin Lou, Jibin Dong, Yali Li, Tingbo Ding, Tingting Bi, Yue Li, Xiaodong Deng, Deyong Ye, Xian-Cheng Jiang |
Jazyk: |
angličtina |
Rok vydání: |
2014 |
Předmět: |
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Zdroj: |
PLoS ONE, Vol 9, Iss 7, p e102641 (2014) |
Druh dokumentu: |
article |
ISSN: |
1932-6203 |
DOI: |
10.1371/journal.pone.0102641 |
Popis: |
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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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