Enhanced sphingomyelinase activity contributes to the apoptotic capacity of electronegative low-density lipoprotein

Ke, Liang-Yin and Chan, Hua-Chen and Chen, Chih-Chieh and Lu, Jonathan and Marathe, Gopal K. and Chu, Chih-Sheng and Chan, Hsiu-Chuan and Wang, Chung-Ya and Tung, Yi-Ching and McIntyre, Thomas M. and Yen, Jeng-Hsien and Chen, Chu-Huang (2016) Enhanced sphingomyelinase activity contributes to the apoptotic capacity of electronegative low-density lipoprotein. Journal of Medicinal Chemistry, 59 (3). pp. 1032-1040. ISSN 1520-4804

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Official URL: https://doi.org/10.1021/acs.jmedchem.5b01534

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/MSE), 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.

Item Type: Article
Additional Information: PMID: 26766134
Subjects: C Chemical Science > Biochemistry
Divisions: Department of > Biochemistry
Depositing User: manjula User
Date Deposited: 28 Jun 2019 09:28
Last Modified: 28 Jun 2019 09:28
URI: http://eprints.uni-mysore.ac.in/id/eprint/4051

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