Histone Deacetylase Inhibitor (SAHA) Reduces Mortality in an Endotoxemia Mouse Model by Suppressing Glycolysis

• DOI: 10.3390/ijms241512448
• Publication Date: 2023-08-05T14:21:39Z
• Authors: Yunchen Wu; Yudan He; Chen Liu; Charlotte Ehle; Aishwarya Iyer-Bi...; Bing Liu; Thorsten Heinzel; Shaojun Xing
• Keywords: Histone deacetylase inhibitor

Sepsis is a life-threatening medical emergency triggered by excessive inflammation in response to an infection. High mortality rates and limited therapeutic options pose significant challenges sepsis treatment. Histone deacetylase inhibitors (HDACi), such as suberoylanilide hydroxamic acid (SAHA), have been proposed potent anti-inflammatory agents for treating inflammatory diseases. However, the underlying mechanisms of treatment remain poorly understood. In this study, we investigated effects SAHA lipopolysaccharide (LPS)-induced endotoxemia mouse model it closely mimics early stages systemic sepsis. Our results demonstrate reduced mediator secretion improved survival mice. Using quantitative acetylomics, found that administration increases acetylation lactate dehydrogenase (LDHA), consequently inhibits LDHA activity. Notably, enzyme activity rate glycolysis. Furthermore, our experiments with bone marrow-derived macrophages (BMDMs) show oxidative stress extracellular ATP concentrations, ultimately blunting inflammasome activation. Overall, study provides insights into mechanism SAHA's highlights potential target developing novel