ABSTRACT
Objective @#To evaluate the change of energy metabolism during cisplatin ⁃induced acute kidney injury.@*Methods @#Adult CD⁃1 male mice were intraperitoneally inj ected 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 ob served swelling and shedding of renal tubular epithelial cells. Transcriptome analysis revealed that 2 632 genes were upregulated and 2 799 genes were downregulated in cisplatin ⁃treated HK⁃2 cells. GO and KEGG analyatin 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.
ABSTRACT
AIM:Chronic exposure to elevated levels of free fatty acids (FFAs) in type 2 diabetes patients is toxic to pancreatic β-cells.Thioredoxin (Trx)-interacting protein (TXNIP), an endogenous Trx-inhibiting protein, is up-regulated by glucose and is a critical mediator of hyperglycemia-induced β-cell apoptosis in diabetes.However, the effects of FFAs on TXNIP are unknown.In this experiment we observed the effect of palmitate on TXNIP expression in cultured INS-1 islet cells and the pathways involved were analyzed meanwhile.METHODS:After the full basis of preliminary experiment of incubating INS-1 cells with palmitate at different concentrations for different time, INS-1 islet cells were cultured with 0.5 mmol/L palmitate for 24 h.TXNIP expression, cell apoptosis, and expression of transcription factors related to TXNIP transcriptional regulation were determined.RESULTS:Compared with control group, the expression of TXNIP at mRNA and protein levels in palmitate group was significantly up-regulated (P<0.01).Cleaved caspase-3/caspase-3 ratio was increased in palmitate group (P<0.05), and the apoptosis of the INS-1 cells was also significantly increased (P<0.01).Palmitate enhanced the phosphorylation of nuclear factor-κB (NF-κB) (P<0.01), and the NF-κB inhibitors, PDTC and SN50, both blocked the palmitate-induced up-regulation of TXNIP expression.CONCLUSION:Saturated fatty acid palmitate enhances the expression of TXNIP.The mechanism of palmitate-induced TXNIP expression may be associa-ted with the increase in NF-κB phosphorylation.