Lactylation in Diabetic Cardiomyopathy

ABSTRACT: Lysine lactylation (Kla), is a newly found post-translational modification that has been found to be involved in the pathogenesis of many diseases. However, the specific effect of protein lactylation has not been reported on the development of diabetic cardiomyopathy (DCM). Here, the purpose of this study was determined whether protein lactylation was involved in the progression of DCM. LC-MS/MS was used to perform proteomic and lactate analysis on the heart tissues of db/m mice (Control group) and db/db mice (DCM group). Subsequently, a series of bioinformatics analyses were used to analyze the kla site and Kla modified proteins in two groups, including GO enrichment, KEGG enrichment, LASSO regression, Logistic regression, random forest (RF), VM-Recursive Feature Elimination (SVM-RFE) algorithm, and other analysis methods. The bioinformatics data analysis showed that the Kla sites in the DCM group were more than those in the Control group. In addition, subcellular localization analysis showed that Kla modified proteins were mainly located in mitochondria and cytoplasm. The protein lactylated modification mainly occurred on histone H2, and compared with the Control group, the modification of H4C1-K32 sites was significantly higher in the DCM group. Furthermore, there were 113 significantly modified kla sites corresponding to 78 modified proteins in the DCM group, while there were 37 significantly modified kla sites corresponding to 25 modified proteins in the Control group. These Kla modified proteins were involved in biological processes and pathways related to glucose metabolism and DCM. Finally, five kla sites were selected as candidate sites by using four machine learning methods, namely A2ASS6 _ K928 _ Ttn, A2ASS6 _ K13499 _ Ttn, Q61425 _ K212 _ Hadh, Q8K2B3 _ K517 _ Sdha, and Q9R0Y5 _ K100 _ Ak1. In conclusions, the present study first reported on the combination of lactylome and proteome of DCM, providing a reliable basis for further investigating the roles of Kla and Kla modified proteins in DCM.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart

SUBMITTER: Can Wei  

LAB HEAD: Can Wei

PROVIDER: PXD067368 | Pride | 2026-05-25

REPOSITORIES: Pride