3-deoxyglucosone and AGEs in uremic complications: inactivation of glutathione peroxidase by 3-deoxyglucosone

Kidney Int Suppl. 2001 Feb;78:S37-41. doi: 10.1046/j.1523-1755.2001.59780037.x.

Abstract

3-deoxyglucosone (3-DG) is accumulated not only in uremic serum but also in uremic erythrocytes. 3-DG rapidly reacts with protein amino groups to form advanced glycation end products (AGEs) such as imidazolone, pyrraline, and N(epsilon)-(carboxymethyl)lysine, among which imidazolone is the AGE that is most specific for 3-DG. In diabetes, hyperglycemia enhances the synthesis of 3-DG via the Maillard reaction and the polyol pathway and thereby leads to its high plasma and erythrocyte levels. In uremia, however, the decreased catabolism of 3-DG that may be due to the loss of 3-DG reductase activity in the end-stage kidneys may lead to a high plasma 3-DG level. The elevated 3-DG levels in uremic patients may promote the formation of AGEs such as imidazolone in erythrocytes, aortas, and dialysis-related amyloid deposits. Treatment with an aldose reductase inhibitor reduced the erythrocyte levels of 3-DG and AGEs such as imidazolone in diabetic uremic patients. This finding demonstrates an important role of the polyol pathway in the formation of erythrocyte 3-DG and AGEs. The erythrocyte levels of 3-DG are elevated in not only diabetic uremic but also nondiabetic uremic patients. 3-DG showed some cytotoxicities by inducing intracellular oxidative stress. In contrast, oxidative stress was demonstrated to cause accumulation of intracellular 3-DG. Recently, we have demonstrated that 3-DG inactivates intracellular enzymes such as glutathione peroxidase, a key enzyme in the detoxification of hydrogen peroxide. Thus, intracellular accumulation of 3-DG may enhance oxidative stress by inactivating the antioxidant enzymes. In conclusion, 3-DG may play a principal role in the development of uremic complications, such as dialysis-related amyloidosis, atherosclerosis, and enhanced oxidative stress.

Publication types

  • Review

MeSH terms

  • Amyloidosis / etiology
  • Animals
  • Apoptosis / drug effects
  • Arteriosclerosis / etiology
  • Cell Division / drug effects
  • Deoxyglucose / analogs & derivatives
  • Deoxyglucose / toxicity*
  • Epidermal Growth Factor / biosynthesis
  • Erythrocytes / metabolism
  • Glucose / metabolism
  • Glutathione Peroxidase / antagonists & inhibitors*
  • Glutathione Peroxidase / blood
  • Glutathione Reductase / antagonists & inhibitors
  • Glycation End Products, Advanced / blood*
  • Heparin-binding EGF-like Growth Factor
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Oxidative Stress
  • Uremia / blood*
  • Uremia / complications*

Substances

  • Glycation End Products, Advanced
  • HBEGF protein, human
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • Epidermal Growth Factor
  • Deoxyglucose
  • Glutathione Peroxidase
  • Glutathione Reductase
  • 3-deoxyglucosone
  • Glucose