Enhanced Sphingomyelinase Activity Contributes to the Apoptotic Capacity of Electronegative Low-Density Lipoprotein

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• 作者：Liang-Yin Ke ; Hua-Chen Chan ; Chih-Chieh Chen ; Jonathan Lu ; Gopal K. Marathe ; Chih-Sheng Chu ; Hsiu-Chuan Chan ; Chung-Ya Wang ; Yi-Ching Tung ; Thomas M. McIntyre ; Jeng-Hsien Yen ; Chu-Huang Chen
• 刊名：Journal of Medicinal Chemistry
• 出版年：2016
• 出版时间：February 11, 2016
• 年：2016
• 卷：59
• 期：3
• 页码：1032-1040
• 全文大小：545K
• ISSN：1520-4804

文摘

Sphingomyelinase (SMase) catalyzes the degradation of sphingomyelin to ceramide. In patients with metabolic syndrome or diabetes, circulating plasma ceramide levels are significantly higher than in normal individuals. Our data indicate that electronegative low-density lipoprotein (LDL) shows SMase activity, which leads to increased ceramide levels that can produce pro-inflammatory effects and susceptibility to aggregation. According to sequence alignment and protein structure predictions, the putative catalytic site of SMase activity is in the α₂ region of apoB-100. To identify specific post-translational modifications of apoB100 near the catalytic region, we performed data-independent, parallel-fragmentation liquid chromatography/mass spectrometry (LC/MS^E), followed by data analysis with ProteinLynx GlobalServer v2.4. Results showed that the serine of apoB100 in electronegative LDL was highly O-glycosylated, including S¹⁷³², S¹⁹⁵⁹, S²³⁷⁸, S²⁴⁰⁸, and S²⁴²⁹. These findings may support the changing of the α-helix/β-pleated sheets ratio in protein structure analysis. Further study is necessary to confirm the activation of SMase activity by electronegative LDL.