Pharmacologic Inhibition of Sphingomyelin Synthase SMS Activity Reduces Apolipoprotein-B Secretion from Hepatocytes and Attenuates Endotoxin-Mediated Macrophage InflammationReport as inadecuate




Pharmacologic Inhibition of Sphingomyelin Synthase SMS Activity Reduces Apolipoprotein-B Secretion from Hepatocytes and Attenuates Endotoxin-Mediated Macrophage Inflammation - Download this document for free, or read online. Document in PDF available to download.

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.



Author: Bin Lou , Jibin Dong , Yali Li , Tingbo Ding, Tingting Bi, Yue Li, Xiaodong Deng, Deyong Ye , Xian-Cheng Jiang

Source: http://plos.srce.hr/



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