Changes in renal cell glycolysis and amino acid metabolism during cisplatin-induced acute kidney injury

Acta Universitatis Medicinalis Anhui 2024 05 v.59 747-752+760     font:big middle small

Found programs:

Authors:Xu Shen; Liang Nannan; Ren Yahui; He Yizhang; Zhang Tao; Yu Dexin

Keywords:cisplatin;acute kidney injury;cellular metabolism;glycolysis;amino acid metabolism

DOI:10.19405/j.cnki.issn1000-1492.2024.05.001

〔Abstract〕 Objective To evaluate the change of energy metabolism during cisplatin-induced acute kidney injury. Methods Adult CD-1 male mice were intraperitoneally injected with a single dose of cisplatin(20 mg/kg), and renal function and renal tissue pathology were tested; gene expression was analyzed and signaling pathways were enriched in cisplatin-treated renal tubular epithelial cells using transcriptome; the contents of renal glycolysis and amino acid metabolites were analyzed using liquid chromatography-tandem mass spectrometry(LC-MS/MS). Results Serum urea nitrogen and blood creatinine significantly increased in cisplatin-treated mice. Pathological histology observed swelling and shedding of renal tubular epithelial cells. Transcriptome analysis revealed that 2 632genes were upregulated and 2 799 genes were downregulated in cisplatin-treated HK-2 cells. GO and KEGG analysis showed that differential genes were enriched in energy metabolism. The GSEA analysis results showed that cisplatin caused an upregulation of the oxidative phosphorylation pathway and a downregulation of the glycolysis pathway in renal tubular epithelial cells, further KEGG analysis demonstrated that cisplatin caused changes in the expression of amino acid genes in renal cells. Metabolomics showed that the contents of glycolytic intermediates and several amino acids were altered in the kidney of cisplatin-treated mice. Conclusion Cisplatin-induced acute renal injury is accompanied by modification in renal tubular cell glycolysis and amino acid metabolism.