Quantitative proteomics reveals key proteins regulated by eicosapentaenoic acid in endothelial activation

Lu Zhang, Kunhong Xiao, Xuyang Zhao, Xiaoli Sun, Jianshu Zhang, Xian Wang, Yi Zhu, Xu Zhang

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Eicosapentaenoic acid (EPA), an n-3 polyunsaturated fatty acid (PUFA), has been shown to decrease the risk of atherosclerosis by attenuating endothelial activation. In this study, we used mass spectrometry-based label-free quantitative proteomics to study the protective mechanisms of EPA and to identify key proteins that regulated by EPA in endothelial activation. Arachidonic acid (AA) was used as a control. HUVECs were pretreated with each of the two PUFAs, and then stimulated with TNFα as a model of endothelial activation. A total of 3391 proteins were identified, and 1958 proteins were quantified. Pearson's correlation coefficients revealed the excellent biological reproducibility of the proteomic results. Gene Ontology and KEGG enrichment analysis of differentially expressed proteins was performed, thus leading to the identification of the glutathione metabolism, oxidation reduction, and DNA replication as the most significantly enriched pathways. Seven key proteins were identified: elongation factor Tu (mitochondrial, TUFM), integrin alpha 6 (ITGA6), catalase (CAT), annexin A6 (ANXA6), heat shock 70 kDa protein 1A (HSPA1A), glutamate-cysteine ligase regulatory subunit (GCLM), and heme oxygenase 1 (HMOX1). Further connections among these proteins were also revealed by protein-protein interaction analysis. The mRNA levels of CAT, GCLM, and HMOX1 were verified with real-time PCR. The protein level of CAT was verified using Western blotting. This study is an in-depth proteomics analysis of EPA-treated cells and may provide possible insights into the molecular mechanisms of EPA's cytoprotective and atheroprotective effects.

Original languageEnglish (US)
Pages (from-to)464-469
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume487
Issue number2
DOIs
StatePublished - May 27 2017
Externally publishedYes

Keywords

  • Arachidonic acid (AA)
  • Atherosclerosis
  • Eicosapentaenoic acid (EPA)
  • Endothelial activation
  • Proteomics
  • Tumor necrosis factor-α (TNFα)

ASJC Scopus subject areas

  • Molecular Biology
  • Biophysics
  • Biochemistry
  • Cell Biology

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