The effect of dicarbonyl stress on the development of kidney dysfunction in metabolic syndrome - a transcriptomic and proteomic approach

Nutrition & Metabolism
I MarkovaH Malinska

Abstract

Dicarbonyl stress plays an important role in the pathogenesis of microvascular complications that precede the formation of advanced glycation end products, and contributes to the development of renal dysfunction. In renal cells, toxic metabolites like methylglyoxal lead to mitochondrial dysfunction and protein structure modifications.In our study, we investigated the effect of methylglyoxal on metabolic, transcriptomic, metabolomic and proteomic profiles in the context of the development of kidney impairment in the model of metabolic syndrome. Dicarbonyl stress was induced by intragastric administration of methylglyoxal (0.5 mg/kg bw for 4 weeks) in a strain of hereditary hypertriglyceridaemic rats with insulin resistance and fatty liver. Methylglyoxal administration aggravated glucose intolerance (AUC0-120p < 0.05), and increased plasma glucose (p < 0.01) and insulin (p < 0.05). Compared to controls, methylglyoxal-treated rats exhibited microalbuminuria (p < 0.01). Targeted proteomic analysis revealed increases in urinary secretion of pro-inflammatory parameters (MCP-1, IL-6, IL-8), specific collagen IV fragments and extracellular matrix proteins. Urine metabolomic biomarkers in methylglyoxal-treated rats were mainly associate...Continue Reading

References

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Datasets Mentioned

BETA
E-MTAB-7690

Methods Mentioned

BETA
ELISA
PCR
biopsies

Software Mentioned

XLSTAT
ADDITION
DK
PARTEK Genomics Suite
Ingenuity Pathway Analysis
GraphPad InStat
Ingenuity Pathway Analysis ( IPA

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