HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 289/2/F420    most recent 00415.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (46) Citing Articles via Google Scholar Google Scholar Articles by Rosca, M. G. Articles by Weiss, M. F. Search for Related Content PubMed PubMed Citation Articles by Rosca, M. G. Articles by Weiss, M. F.

Glycation of mitochondrial proteins from diabetic rat kidney is associated with excess superoxide formation

Departments of ¹Medicine, ²Pathology and Biochemistry, and ⁴Physiology, Case Western Reserve University, and ³Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio; and ⁵Department of Medicine and Pathology and Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, New York

Submitted 19 November 2004 ; accepted in final form 29 March 2005

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 -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.

methylglyoxal; nephropathy; complex III; proteomics

This article has been cited by other articles:

				N. Frizzell, M. Rajesh, M. J. Jepson, R. Nagai, J. A. Carson, S. R. Thorpe, and J. W. Baynes Succination of Thiol Groups in Adipose Tissue Proteins in Diabetes: SUCCINATION INHIBITS POLYMERIZATION AND SECRETION OF ADIPONECTIN J. Biol. Chem., September 18, 2009; 284(38): 25772 - 25781. [Abstract] [Full Text] [PDF]

				M. T. Coughlan, D. R. Thorburn, S. A. Penfold, A. Laskowski, B. E. Harcourt, K. C. Sourris, A. L.Y. Tan, K. Fukami, V. Thallas-Bonke, P. P. Nawroth, et al. RAGE-Induced Cytosolic ROS Promote Mitochondrial Superoxide Generation in Diabetes J. Am. Soc. Nephrol., April 1, 2009; 20(4): 742 - 752. [Abstract] [Full Text] [PDF]

				J. M. Forbes, M. T. Coughlan, and M. E. Cooper Oxidative Stress as a Major Culprit in Kidney Disease in Diabetes Diabetes, June 1, 2008; 57(6): 1446 - 1454. [Abstract] [Full Text] [PDF]

				H. Al-Kateb, A. P. Boright, L. Mirea, X. Xie, R. Sutradhar, A. Mowjoodi, B. Bharaj, M. Liu, J. M. Bucksa, V. L. Arends, et al. Multiple Superoxide Dismutase 1/Splicing Factor Serine Alanine 15 Variants Are Associated With the Development and Progression of Diabetic Nephropathy: The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Genetics Study Diabetes, January 1, 2008; 57(1): 218 - 228. [Abstract] [Full Text] [PDF]

				E. M. V. de Cavanagh, L. Ferder, J. E. Toblli, B. Piotrkowski, I. Stella, C. G. Fraga, and F. Inserra Renal mitochondrial impairment is attenuated by AT1 blockade in experimental Type I diabetes Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H456 - H465. [Abstract] [Full Text] [PDF]

				M. Kanwar, P.-S. Chan, T. S. Kern, and R. A. Kowluru Oxidative Damage in the Retinal Mitochondria of Diabetic Mice: Possible Protection by Superoxide Dismutase Invest. Ophthalmol. Vis. Sci., August 1, 2007; 48(8): 3805 - 3811. [Abstract] [Full Text] [PDF]

				M. G. Janech, J. R. Raymond, and J. M. Arthur Proteomics in renal research Am J Physiol Renal Physiol, February 1, 2007; 292(2): F501 - F512. [Abstract] [Full Text] [PDF]

				A. Riboulet-Chavey, A. Pierron, I. Durand, J. Murdaca, J. Giudicelli, and E. Van Obberghen Methylglyoxal impairs the insulin signaling pathways independently of the formation of intracellular reactive oxygen species. Diabetes, May 1, 2006; 55(5): 1289 - 1299. [Abstract] [Full Text] [PDF]

				H. Liu, F. Zheng, Q. Cao, B. Ren, L. Zhu, G. Striker, and H. Vlassara Amelioration of oxidant stress by the defensin lysozyme Am J Physiol Endocrinol Metab, May 1, 2006; 290(5): E824 - E832. [Abstract] [Full Text] [PDF]