|Glycation of mitochondrial proteins from diabetic rat kidney is associated with excess superoxide formation.|
|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|
Related Documents :
|25383099 - Correlation between reduction of superior interventricular groove epicardial fat thickn...
10536489 - The effect of glycosaminoglycan sulodexide on oxidative stress and fibrinolysis in diab...
19345729 - Oxidative stress and the development of diabetic retinopathy: contributory role of matr...
8983089 - Hormonal response to stress in brittle diabetes.
16949779 - Protective effect of the chinese prescription kangen-karyu against high glucose-induced...
22237689 - How much does screening bring forward the diagnosis of type 2 diabetes and reduce compl...
3902039 - Changes in insulin therapy during pregnancy.
3328719 - The effects of insulin-induced hypoglycaemia on cardiovascular function in normal man: ...
8735189 - Endothelin-1-induced modulation of contractile responses elicited by an alpha 1-adrener...
|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|
|Title: American journal of physiology. Renal physiology Volume: 289 ISSN: 1931-857X ISO Abbreviation: Am. J. Physiol. Renal Physiol. Publication Date: 2005 Aug|
|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|
|Languages: eng Pagination: F420-30 Citation Subset: IM|
|Deparment of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.|
|APA/MLA Format Download EndNote Download BibTex|
Blood Glucose / metabolism
Diabetes Mellitus, Experimental / metabolism
Diabetic Nephropathies / metabolism*
Electrophoresis, Gel, Two-Dimensional
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 Stress / drug effects
Oxygen Consumption / drug effects
Pyruvaldehyde / pharmacology
Rats, Inbred Lew
Superoxides / metabolism*
Uncoupling Agents / pharmacology
|DK-45619/DK/NIDDK NIH HHS; DK-57733/DK/NIDDK NIH HHS; ES-11461/ES/NIEHS NIH HHS|
|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|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Exaggerated response to adenosine in kidneys from high salt-fed rats: role of epoxyeicosatrienoic ac...
Next Document: Nedd4-2 isoforms differentially associate with ENaC and regulate its activity.