We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
AST-120 alleviates renal ischemia-reperfusion injury by inhibiting HK2-mediated glycolysis.
- Authors
Zhou, Jinmeng; Zhang, Jinbao; Xu, Feng; Gao, Haijin; Wang, Lei; Zhao, Yutong; Li, Ke
- Abstract
Objective: Renal 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. Methods: A 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. Results: The 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. Conclusions: In 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.
- Subjects
GENE expression; ACUTE kidney failure; KIDNEY physiology; REPERFUSION injury; RNA sequencing
- Publication
Molecular Medicine, 2024, Vol 30, Issue 1, p1
- ISSN
1076-1551
- Publication type
Article
- DOI
10.1186/s10020-024-00902-y