Proteomic analysis defines altered cellular redox pathways and advanced glycation end-product metabolism in glomeruli of db/db diabetic mice.

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Barati MT, Merchant ML, Kain AB, Jevans AW, McLeish KR, Klein JB

Proteomic analysis defines altered cellular redox pathways and advanced glycation end-product metabolism in glomeruli of db/db diabetic mice.

Am J Physiol Renal Physiol. 2007 Oct;293(4):F1157-65. Epub 2007 Jul 3.

PubMed ID

17609286 [ View in PubMed

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Abstract

To attain a profile of protein expression during diabetes, we applied proteomic analysis to glomeruli of 160-day-old db/db diabetic and db/m nondiabetic mice. Glomerular proteins were extracted and separated by two-dimensional gel electrophoresis to construct a proteome map. Matrix-assisted laser desorption and ionization-time of flight mass spectrometry and peptide mass fingerprinting were used to identify 190 proteins. Of 105 analyzed spots, expression of 40 proteins, including the antioxidative enzymes peroxiredoxin 1 and 3, glutathione peroxidase 1, and SOD-1, was increased with diabetes, suggesting an adaptive response to oxidative stress associated with this diabetic model. However, activity of glutathione peroxidase and SOD was unaltered in glomeruli of diabetic mice. Expression of glyoxalase I was increased in glomeruli of diabetic mice. Because the cofactor for glyoxalase I, glutathione, is decreased in renal cortex of db/db mice, renal cortical glyoxalase I activity was measured in vitro with fixed amounts of exogenous glutathione. Glyoxalase I activity was decreased in renal cortex of db/db mice. These data indicate that diabetes-induced decreases in glyoxalase I activity are likely to be due to glutathione-dependent and -independent mechanisms and that increased expression of glyoxalase I may represent an insufficient adaptive response to increased methylglyoxal formation.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Glutathione	Lactoylglutathione lyase	Protein	Humans	Unknown	Not Available	Details