AUTHOR=Luo Weiguang , He Mei , Luo Qizhi , Li Yi 

TITLE=Proteome-wide analysis of lysine β-hydroxybutyrylation in the myocardium of diabetic rat model with cardiomyopathy

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 9 - 2022

YEAR=2023

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.1066822

DOI=10.3389/fcvm.2022.1066822

ISSN=2297-055X

ABSTRACT=Lysineβ-hydroxybutyrylation (kbhb), a novel identified protein post-translational modification (PTM) of lysine residues withβ-hydroxybuty group, has been proved to be associated with ketone metabolism and is present in numerous species. However, its potential roles in diabetes, especially in diabetic cardiomyopathy (DCM), remains largely unexplored. In this study, we performed antibody-based affinity Enrichment and Liquid chromatography-mass spectrometry (LC-MS/MS) to quantitatively analyze kbhb residues on heart tissues of both wild type and established DCM model rat. A total of 3520 lysine sites in 1089 proteins identified in this study were found to be β-hydroxybutyrylated. Further analysis shown that 336 Kbhb sites in 143 proteins that were differentially expressed in heart tissues of DCM rats. Among them, 284 Kbhb sites in 96 proteins were found increased while 52 Kbhb sites in 47 proteins were found decreased. Bioinformatic analysis of the proteomic results revealed that the up-regulated proteins in heart tissues of DCM rats were mainly located in cytoplasm, whereas the down-regulated Kbhb proteins were mainly distributed in mitochondria. Functional enrichment analysis shown that up-regulated proteins were enriched in tricarboxylic acid cycle, oxidative phosphorylation and propanoate metabolism, while the down-regulated proteins were enriched in cGMP-PKG signaling pathway and glutathione metabolism. Our findings demonstrated that Kbhb is related to many metabolic pathways, especially those involved in energy metabolism. Taken together, this study provides the first global investigation of Kbhb profile in the progression of DCM and should be an important resource to further explore the pathogenesis of DCM.