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Quantitative proteomics profiling of lysine 2‐hydroxyisobutyrylation in right atrial appendage from rheumatic heart valve disease patients
Author(s) -
Hou HaiTao,
Yang Qin,
He GuoWei
Publication year - 2022
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2022.36.s1.r2835
Subject(s) - proteomics , chemistry , lysine , tandem mass spectrometry , kegg , biochemistry , biology , gene , gene expression , amino acid , transcriptome , mass spectrometry , chromatography
Objectives Lysine 2‐hydroxyisobutyrylation (K hib ) is a novel acylation that regulates glycolysis. Little has been done in human diseases regarding the role of K hib . The present study was designed to reveal the role of K hib in the development of atrial fibrillation (AF) associated with heart valve disease. Methods Discarded right atrial appendage tissues during the cannulation procedure were collected from AF and sinus rhythm (SR) patients with rheumatic heart valve disease. The protein profiles and K hib sites were identified and qualified by Tandem Mass Tag labeling and liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) technology. Bioinformatic tools, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein‐protein interaction, were also used to explore the biological function between AF and SR. Results A total of 6,523 matched spectrum, 3,234 peptides, 2,867 modified peptides, corresponding to 579 proteins and 2,900 sites from LC‐MS/MS analysis were identified. Of these identified proteins and sites, 480 proteins and 2,275 sites were quantifiable. The length of most peptides distributed between 7 and 22, which was consistent with the length of tryptic peptides. Differentially expressed K hib sites analysis showed that there were 35 and 48 K hib sites related to 124 and 67 proteins exhibited upregulation and downregulation in AF compared to SR. Subcellular location analysis of K hib ‐related proteins revealed that cytoplasm, nucleus, and extracellular accounted for the most proportion. Bioinformatic analysis demonstrated that proteins with K hib were significantly enriched in different biological approach, such as cysteine and methionine metabolism, cGMP‐PKG signaling pathway, and glucose‐responsive energy metabolism. Conclusions The present study for the first time revealed larger number of differentially expressed K hib sites between AF and SR in patients with rheumatic valve disease. The proteins related to these sites are involved in diverse cellular processes including energy metabolism. These results indicate that K hib modification might be a key factor in occurrence of AF in patients with rheumatic heart valve disease.