title: Enhanced Sphingomyelinase Activity Contributes to the Apoptotic Capacity of Electronegative Low-Density Lipoprotein.
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.
authors.affiliation: Vascular and Medicinal Research, Texas Heart Institute , Houston, Texas 77030, United States.
authors.forename: Liang-Yin
authors.initials: LY
authors.lastname: Ke
authors.affiliation: Vascular and Medicinal Research, Texas Heart Institute , Houston, Texas 77030, United States.
authors.forename: Hua-Chen
authors.initials: HC
authors.lastname: Chan
authors.affiliation: Institute of Medical Science and Technology, National Sun Yat-sen University , Kaohsiung, Taiwan 80424.
authors.forename: Chih-Chieh
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Vascular and Medicinal Research, Texas Heart Institute , Houston, Texas 77030, United States.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Lu
authors.affiliation: Departments of Cellular & Molecular Medicine, Lerner Research Institute, Cleveland Clinic Lerner College of Medicine , Cleveland, Ohio 44195, United States.|Department of Studies in Biochemistry, Manasagangothri, University of Mysore , Mysore-570006, India.
authors.forename: Gopal K
authors.initials: GK
authors.lastname: Marathe
authors.forename: Chih-Sheng
authors.initials: CS
authors.lastname: Chu
authors.forename: Hsiu-Chuan
authors.initials: HC
authors.lastname: Chan
authors.forename: Chung-Ya
authors.initials: CY
authors.lastname: Wang
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Tung
authors.affiliation: Departments of Cellular & Molecular Medicine, Lerner Research Institute, Cleveland Clinic Lerner College of Medicine , Cleveland, Ohio 44195, United States.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: McIntyre
authors.forename: Jeng-Hsien
authors.initials: JH
authors.lastname: Yen
authors.affiliation: Vascular and Medicinal Research, Texas Heart Institute , Houston, Texas 77030, United States.|New York Heart Research Foundation, Mineola, New York 11501, United States.
authors.forename: Chu-Huang
authors.initials: CH
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000166:cytology / Q000201:enzymology; D013329:Structure-Activity Relationship
chemical_list: D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D013108:Sphingomyelin Phosphodiesterase