ArticleInternational journal of molecular sciences2023
Histone Deacetylase Inhibitor (SAHA) Reduces Mortality in an Endotoxemia Mouse Model by Suppressing Glycolysis.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- Lactylation: a promising target for musculoskeletal disorders via interactions with chronic inflammation.Journal of advanced research · 2026Review
- Integrative metabolite-protein interaction networks reveal potential pathways and biomarkers in sepsis.BMC infectious diseases · 2026Article
- Proof-of-concept study: APOE4 brain endothelial cells as a phenotypic compound screen.Alzheimer's research & therapy · 2026Article
- Interaction networks of macrophage glycolysis and inflammation in sepsis: mechanisms and therapeutic potential.Frontiers in immunology · 2026Review
- Immunometabolic Reprogramming in Experimental Sepsis: A Driver of Multiple Organ Dysfunction Syndrome.Journal of inflammation research · 2026Review
- The Roles of Histone H3K18 Lactylation, Acetylation, and Lactylation/Acetylation Ratio as Potential Biomarkers in the Diagnosis and Severity Assessment of Sepsis and Septic Shock.Infectious diseases and therapy · 2025Article
- Lactate, an Essential Metabolic Marker in the Diagnosis and Management of Pediatric Conditions.Diagnostics (Basel, Switzerland) · 2025Review
- Progress in Lactate Metabolism and Its Regulation via Small Molecule Drugs.Molecules (Basel, Switzerland) · 2024Review
- Post-translational modifications in sepsis-induced organ dysfunction: mechanisms and implications.Frontiers in immunology · 2024Review
- The lactate metabolism and protein lactylation in epilepsy.Frontiers in cellular neuroscience · 2024Review
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
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 in sepsis treatment. Histone deacetylase inhibitors (HDACi), such as suberoylanilide hydroxamic acid (SAHA), have been proposed as potent anti-inflammatory agents for treating inflammatory diseases. However, the underlying mechanisms of sepsis treatment remain poorly understood. In this study, we investigated the effects of SAHA treatment in the lipopolysaccharide (LPS)-induced endotoxemia mouse model as it closely mimics the early stages of the systemic inflammation of sepsis. Our results demonstrate a reduced inflammatory mediator secretion and improved survival rates in mice. Using quantitative acetylomics, we found that SAHA administration increases the acetylation of lactate dehydrogenase (LDHA), and consequently inhibits LDHA activity. Notably, the reduced enzyme activity of LDHA results in a reduced rate of glycolysis. Furthermore, our experiments with bone marrow-derived macrophages (BMDMs) show that SAHA administration reduced oxidative stress and extracellular ATP concentrations, ultimately blunting inflammasome activation. Overall, our study provides insights into the mechanism underlying SAHA's therapeutic effects in sepsis treatment and highlights LDHA as a potential target for developing novel sepsis treatment.
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Registered trials
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