ArticleMolecular medicine (Cambridge, Mass.)2024
AST-120 alleviates renal ischemia-reperfusion injury by inhibiting HK2-mediated glycolysis.
Article in Molecular medicine (Cambridge, Mass.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Advancements in early biomarkers of acute kidney injury: from traditional indicators to a paradigm shift in lactate metabolism.Annals of medicine · 2026Review
- Metabolic memory in the kidney: how lactate and lactylation drive the path from acute injury to chronic disease.Renal failure · 2026Review
- The mechanism and therapeutic prospect of HIF-1 α/BNIP3 pathway in regulating mitophagy in tubulointerstitial fibrosis.Renal failure · 2026Review
- The lactate-lactylation axis in acute kidney injury: mechanisms from metabolic reprogramming to epigenetic regulation and clinical therapeutic prospects.International urology and nephrology · 2026Review
- Interplay between ischemia-reperfusion and metabolic reprogramming.Apoptosis : an international journal on programmed cell death · 2026Review
- From lactate to lactylation: novel pathological mechanisms and potential therapeutic targets for high-altitude cerebral oedema.Expert reviews in molecular medicine · 2026Review
- ChIP-seq and RNA-seq Reveal the Involvement of Histone Lactylation Modification in Early Pregnancy with Subclinical Hypothyroidism.Biochemical genetics · 2026Article
- Lactylation in tissue fibrosis: epigenetic mechanisms, metabolic crosstalk, and therapeutic opportunities.Journal of translational medicine · 2026Review
- Rutin as a Potential Therapeutic Agent for Multi-Organ Ischemia-Reperfusion Injury: From Multidimensional Mechanisms to Clinical Translation.Molecules (Basel, Switzerland) · 2026Review
- Glycolysis enzymes and cellular lactylation in tumour.Clinical and translational medicine · 2026Review
- Mechanistic elucidation of Wuling Powder targeting macrophage polarization to ameliorate renal ischemia-reperfusion injury via multidimensional computational systems pharmacology coupled with experimental validation.Frontiers in pharmacology · 2026Article
- Lactylation in kidney diseases: a review of regulatory mechanisms and therapeutic prospects.Frontiers in cell and developmental biology · 2026Review
- Lactate and Lactylation in AKI-to-CKD: Epigenetic Regulation and Therapeutic Opportunities.Cell proliferation · 2025Review
- Tri-domain proteins 27 alleviates ischemia-reperfusion injury-induced acute kidney injury by promoting Gli-like transcription factor 1 expression via the inhibition of polycomb repressive complex 2 activity.Journal of cell communication and signaling · 2025Article
- Lactylation modifications in urological diseases: molecular mechanisms and biological implications.Clinical epigenetics · 2025Review
- Lactate and lactylation in the kidneys: Current advances and prospects (Review).International journal of molecular medicine · 2025Review
- Protein lactylation in kidney diseases.Frontiers in cell and developmental biology · 2025Review
- Histone Lactylation in Diseases: Regulation by Traditional Chinese Medicine and Therapeutic Implications.Drug design, development and therapy · 2025Review
- Progress in Lactate Metabolism and Its Regulation via Small Molecule Drugs.Molecules (Basel, Switzerland) · 2024Review
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Authors and funding
7 authors.
Funding
Abstract
objectiveRenal ischemia/reperfusion injury (IRI) is a major cause of acute kidney injury (AKI), which is associated with high incidence and mortality. AST-120 is an oral carbonaceous adsorbent that can alleviate kidney damage. This study aimed to explore the effects of AST-120 on renal IRI and the molecular mechanism.
methodsA renal IRI mouse model was established and administrated AST-120, and differentially expressed genes were screened using RNA sequencing. Renal function and pathology were analyzed in mice. Hypoxia/reoxygenation (H/R) cell model was generated, and glycolysis was evaluated by detecting lactate levels and Seahorse analysis. Histone lactylation was analyzed by western blotting, and its relationship with hexokinase 2 (HK2) was assessed using chromatin immunoprecipitation.
resultsThe results showed that HK2 expression was increased after IRI, and AST-120 decreased HK2 expression. Knockout of HK2 attenuated renal IRI and inhibits glycolysis. AST-120 inhibited renal IRI in the presence of HK2 rather than HK2 absence. In proximal tubular cells, knockdown of HK2 suppressed glycolysis and H3K18 lactylation caused by H/R. H3K18 lactylation was enriched in HK2 promoter and upregulated HK2 levels. Rescue experiments revealed that lactate reversed IRI that suppressed by HK2 knockdown.
conclusionsIn conclusion, AST-120 alleviates renal IRI via suppressing HK2-mediated glycolysis, which suppresses H3K18 lactylation and further reduces HK2 levels. This study proposes a novel mechanism by which AST-120 alleviates IRI.
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