Document Detail

Glycation of mitochondrial proteins from diabetic rat kidney is associated with excess superoxide formation.
MedLine Citation:
PMID:  15814529     Owner:  NLM     Status:  MEDLINE    
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.
Mariana G Rosca; Tiberiu G Mustata; Michael T Kinter; Aylin M Ozdemir; Timothy S Kern; Luke I Szweda; Michael Brownlee; Vincent M Monnier; Miriam F Weiss
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2005-04-05
Journal Detail:
Title:  American journal of physiology. Renal physiology     Volume:  289     ISSN:  1931-857X     ISO Abbreviation:  Am. J. Physiol. Renal Physiol.     Publication Date:  2005 Aug 
Date Detail:
Created Date:  2005-07-11     Completed Date:  2005-08-17     Revised Date:  2011-04-28    
Medline Journal Info:
Nlm Unique ID:  100901990     Medline TA:  Am J Physiol Renal Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  F420-30     Citation Subset:  IM    
Deparment of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
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MeSH Terms
2,4-Dinitrophenol / pharmacology
Blood Glucose / metabolism
Blotting, Western
Diabetes Mellitus, Experimental / metabolism
Diabetic Nephropathies / metabolism*
Electrophoresis, Gel, Two-Dimensional
Energy Metabolism
Fatty Acids / metabolism
Glucose / metabolism
Guanidines / pharmacology
Mitochondria / drug effects,  metabolism
Mitochondrial Proteins / drug effects,  metabolism*
Multienzyme Complexes / metabolism
NADH, NADPH Oxidoreductases / metabolism
Oxidants / metabolism*
Oxidative Phosphorylation
Oxidative Stress / drug effects
Oxygen Consumption / drug effects
Pyruvaldehyde / pharmacology
Rats, Inbred Lew
Superoxides / metabolism*
Uncoupling Agents / pharmacology
Grant Support
Reg. No./Substance:
0/Blood Glucose; 0/Fatty Acids; 0/Guanidines; 0/Mitochondrial Proteins; 0/Multienzyme Complexes; 0/Oxidants; 0/Uncoupling Agents; 11062-77-4/Superoxides; 50-99-7/Glucose; 51-28-5/2,4-Dinitrophenol; 78-98-8/Pyruvaldehyde; 79-17-4/pimagedine; EC 1.6.-/NADH oxidase; EC 1.6.-/NADH, NADPH Oxidoreductases

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