Trichostatin A Influences Dendritic Cells’ Functions by Regulating Glucose and Lipid Metabolism via PKM2

TL;DR

This study shows how Trichostatin A affects dendritic cells' function in heart attack recovery by changing their glucose and fat metabolism.

Contribution

The novel finding is that TSA modulates DC metabolism via PKM2, influencing immune protection in myocardial infarction.

Findings

TSA alleviates OGD-induced damage in DCs by modulating glucose and lipid metabolism.

PKM2 is upregulated under OGD and mediates TSA's effects through dimer formation.

TSA enhances glycolysis and suppresses fatty acid synthesis and oxidation in DCs.

Abstract

Dendritic cells (DCs) play a crucial role in immune protection against myocardial infarction (MI). Through multiple experimental methods including bioinformatics, qPCR, Western blotting, immunofluorescence, MTT assays, echocardiography, TTC staining, and flow cytometry, this study found that metabolism was demonstrated to be markedly altered under oxygen–glucose deprivation (OGD) conditions in DCs. Pyruvate kinase M2 (PKM2) is a key protein in metabolism, and PKM2 was upregulated under OGD conditions in DCs. Trichostatin A (TSA) alleviated the OGD-induced cellular damage in DCs. Furthermore, TSA was shown to modulate DCs’ function by enhancing glycolysis while suppressing fatty acid synthesis and oxidation pathways. The metabolic changes caused by TSA and OGD were mechanistically mediated by PKM2. Mechanistically, PKM2 modulates glucose and lipid metabolism via its dimer formation. These results deepen our understanding of the interplay among TSA, glucose and lipid metabolism and DC functions in MI.

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