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

Journal of Medicinal Chemistry
Liang-Yin KeChu-Huang Chen

Abstract

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 S(1732), S(1959), S(2378), S(2408), and S(2429). 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.

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Citations

Mar 31, 2018·Current Medicinal Chemistry·Andrea Rivas-UrbinaJosé Luis Sánchez-Quesada
Jun 6, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Liang-Yin KeChu-Huang Chen
Nov 11, 2020·International Journal of Molecular Sciences·Takashi Obama, Hiroyuki Itabe
Aug 28, 2021·Antioxidants·Jean-Marc ZinggRoberta Ricciarelli

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