Glycation of mitochondrial proteins from diabetic rat kidney is associated with
excess superoxide formation.
Authors Rosca MG, Mustata TG, Kinter MT, Ozdemir AM, Kern TS, Szweda LI, Brownlee M,
Monnier VM, Weiss MF
Submitted By Submitted Externally on 10/1/2015
Status Published
Journal American journal of physiology. Renal physiology
Year 2005
Date Published 8/1/2005
Volume : Pages 289 : F420 - 30
PubMed Reference 15814529
Abstract Chronic hyperglycemia causes structural alterations of proteins through the
Maillard reaction. In diabetes, methylglyoxal (MGO)-induced hydroimidazolones
are the predominant modification. In contrast to acute hyperglycemia,
mitochondrial respiration is depressed in chronic diabetes. To determine whether
MGO-derived protein modifications result in abnormalities in mitochondrial
bioenergetics and superoxide formation, proteomics and functional studies were
performed in renal cortical mitochondria isolated from rats with 2, 6, and 12 mo
of streptozotocin-induced diabetes. MGO-modified proteins belonged to the
following two pathways: 1) oxidative phosphorylation and 2) fatty acid
beta-oxidation. Two of these proteins were identified as components of
respiratory complex III, the major site of superoxide production in health and
disease. Mitochondria from rats with diabetes exhibited a diminution of
oxidative phosphorylation. A decrease in the respiratory complex III activity
was significantly correlated with the quantity of MGO-derived hydroimidazolone
present on mitochondrial proteins in both diabetic and control animals. In
diabetes, isolated renal mitochondria produced significantly increased
quantities of superoxide and showed evidence of oxidative damage. Administration
of aminoguanidine improved mitochondrial respiration and complex III activity
and decreased oxidative damage to mitochondrial proteins. Therefore,
posttranslational modifications of mitochondrial proteins by MGO may represent
pathogenic events leading to mitochondria-induced oxidative stress in the kidney
in chronic diabetes.

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