Untitled

Abstract

Receptors for advanced glycation end products (RAGE), which bind and internalize AGE-modified proteins formed from oxidation and other products of the nonenzymatic glycation reaction, have been mechanistically implicated in the development of the chronic complications of diabetes. In the present experiments, we sought evidence for the participation of RAGE in diabetic nephropathy by analysis of steady state levels of mRNA encoding RAGE in the renal cortex of a well-defined animal model (the db/db mouse) that develops renal pathology similar to that found in human diabetes. In these animals, increased AGE-product formation was confirmed by measurement of fluorescence in serum and renal cortex proteins. Renal involvement was confirmed by demonstration of increased urine albumin excretion and elevated serum creatinine concentrations relative to nondiabetic (db/m) littermate controls. Despite elevated concentrations of circulating and tissue AGE-modified proteins, the level of RAGE mRNA expression in renal cortex of diabetic mice did not significantly differ from that in nondiabetic littermate controls. The findings militate against changes in RAGE expression in the pathogenesis of renal abnormalities in this animal model.

Diphlorethohydroxycarmalol Attenuates Methylglyoxal‐Induced Oxidative Stress and Advanced Glycation End Product Formation in Human Kidney Cells

“…DPHC treatment did not affect the expression of RAGE mRNA, suggesting that a decrease in the accumulated amount of AGE might contribute to the preventive effects on MGO-induced cytotoxicity. In agreement with this result, it was reported that circulating and tissue levels of AGE-modified proteins were increased in diabetic db/db mice, but RAGE expression levels in the renal cortex were not different between diabetic and nondiabetic littermates [ 67 ].…”

Novel Interplay Between Smad1 and Smad3 Phosphorylation via AGE Regulates the Progression of Diabetic Nephropathy

“…S2a,b ). Activation of the AGE/RAGE/NFκB pathway may play an important role in the pathogenesis of the DN 26 , 29 . To verify that AGE-RAGE signal activation, we assessed the expression and phosphorylation (activation) status of NFκB subunit p65.…”

“…Concentrations of AGE-modified plasma and renal proteins were determined by measurement of fluorescence using an excitation wavelength of 340 nm and an emission wavelength of 415 nm as described elsewhere 29 . Measurement of protein concentration in plasma and in extracts of the renal cortex allowed expression of the data as arbitrary fluorescence units normalized to protein content.…”