2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) 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 PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by SUZUKI, D. Articles by KUROKAWA, K. Search for Related Content PubMed PubMed Citation Articles by SUZUKI, D. Articles by KUROKAWA, K.

Immunohistochemical Evidence for an Increased Oxidative Stress and Carbonyl Modification of Proteins in Diabetic Glomerular Lesions

DAISUKE SUZUKI^*, TOSHIO MIYATA^*, NOBORU SAOTOME^*, KATSUNORI HORIE^*, REIKO INAGI^*, YOSHINARI YASUDA^*, KOJI UCHIDA, YUKO IZUHARA^*, MITSUNORI YAGAME^*, HIDETO SAKAI^* and KIYOSHI KUROKAWA^*

^* Molecular and Cellular Nephrology, Institute of Medical Sciences and Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan
Laboratory of Food and Biodynamics, Nagoya University School of Agricultural Sciences, Nagoya, Japan.

Correspondence to Dr. Toshio Miyata, Molecular and Cellular Nephrology, Institute of Medical Sciences and Department of Internal Medicine, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259-11, Japan. Phone: 81 463 93 1936; Fax: 81 463 93 1938; E-mail: t-miyata{at}is.icc.u-tokai.ac.jp

Abstract. Advanced glycation end products (AGE) include a variety of protein adducts whose accumulation has been implicated in tissue damage associated with diabetic nephropathy (DN). It was recently demonstrated that among AGE, glycoxidation products, whose formation is closely linked to oxidation, such as carboxymethyllysine (CML) and pentosidine, accumulate in expanded mesangial matrix and nodular lesions in DN, in colocalization with malondialdehyde-lysine (MDA-lysine), a lipoxidation product, whereas pyrraline, another AGE structure whose deposition is rather independent from oxidative stress, was not found within diabetic glomeruli. Because CML, pentosidine, and MDA-lysine are all formed under oxidative stress by carbonyl amine chemistry between protein amino group and carbonyl compounds, their colocalization suggests a local oxidative stress and increased protein carbonyl modification in diabetic glomerular lesions. To address this hypothesis, human renal tissues from patients with DN or IgA nephropathy were examined with specific antibodies to characterize most, if not all, carbonyl modifications of proteins by autoxidation products of carbohydrates, lipids, and amino acids: CML (derived from carbohydrates, lipids, and amino acid), pentosidine (derived from carbohydrates), MDA-lysine (derived from lipids), 4-hydroxynonenal-protein adduct (derived from lipids), and acrolein-protein adduct (derived from lipids and amino acid). All of the protein adducts were identified in expanded mesangial matrix and nodular lesions in DN. In IgA nephropathy, another primary glomerular disease leading to end-stage renal failure, despite positive staining for MDA-lysine and 4-hydroxynonenal-protein adduct in the expanded mesangial area, CML, pentosidine, and acrolein-protein adduct immunoreactivities were only faint in glomeruli. These data suggest a broad derangement in nonenzymatic biochemistry in diabetic glomerular lesions, and implicate an increased local oxidative stress and carbonyl modification of proteins in diabetic glomerular tissue damage ("carbonyl stress").

This article has been cited by other articles:

				E. Nerpin, U. Riserus, E. Ingelsson, J. Sundstrom, M. Jobs, A. Larsson, S. Basu, and J. Arnlov Insulin Sensitivity Measured With Euglycemic Clamp Is Independently Associated With Glomerular Filtration Rate in a Community-Based Cohort Diabetes Care, August 1, 2008; 31(8): 1550 - 1555. [Abstract] [Full Text] [PDF]

				M. Buleon, J. Allard, A. Jaafar, F. Praddaude, Z. Dickson, M.-T. Ranera, C. Pecher, J.-P. Girolami, and I. Tack Pharmacological blockade of B2-kinin receptor reduces renal protective effect of angiotensin-converting enzyme inhibition in db/db mice model Am J Physiol Renal Physiol, May 1, 2008; 294(5): F1249 - F1256. [Abstract] [Full Text] [PDF]

				S. Ohtomo, M. Nangaku, Y. Izuhara, S. Takizawa, C. v. Y. d. Strihou, and T. Miyata Cobalt ameliorates renal injury in an obese, hypertensive type 2 diabetes rat model Nephrol. Dial. Transplant., April 1, 2008; 23(4): 1166 - 1172. [Abstract] [Full Text] [PDF]

				N. Shanmugam, J. L. Figarola, Y. Li, P. M. Swiderski, S. Rahbar, and R. Natarajan Proinflammatory Effects of Advanced Lipoxidation End Products in Monocytes Diabetes, April 1, 2008; 57(4): 879 - 888. [Abstract] [Full Text] [PDF]

				A. Goldin, J. A. Beckman, A. M. Schmidt, and M. A. Creager Advanced Glycation End Products: Sparking the Development of Diabetic Vascular Injury Circulation, August 8, 2006; 114(6): 597 - 605. [Abstract] [Full Text] [PDF]

				M. Nangaku, Y. Izuhara, N. Usuda, R. Inagi, T. Shibata, S. Sugiyama, K. Kurokawa, C. van Ypersele de Strihou, and T. Miyata In a type 2 diabetic nephropathy rat model, the improvement of obesity by a low calorie diet reduces oxidative/carbonyl stress and prevents diabetic nephropathy Nephrol. Dial. Transplant., December 1, 2005; 20(12): 2661 - 2669. [Abstract] [Full Text] [PDF]

				S. Genuth, W. Sun, P. Cleary, D. R. Sell, W. Dahms, J. Malone, W. Sivitz, V. M. Monnier, and for the DCCT Skin Collagen Ancillary Study Group Glycation and Carboxymethyllysine Levels in Skin Collagen Predict the Risk of Future 10-Year Progression of Diabetic Retinopathy and Nephropathy in the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications Participants With Type 1 Diabetes Diabetes, November 1, 2005; 54(11): 3103 - 3111. [Abstract] [Full Text] [PDF]

				J. M. Bohlender, S. Franke, G. Stein, and G. Wolf Advanced glycation end products and the kidney Am J Physiol Renal Physiol, October 1, 2005; 289(4): F645 - F659. [Abstract] [Full Text] [PDF]

				K. Zitouni, J. Nourooz-Zadeh, D. Harry, S. M. Kerry, D. J. Betteridge, F. P. Cappuccio, and K. A. Earle Race-Specific Differences in Antioxidant Enzyme Activity in Patients With Type 2 Diabetes: A potential association with the risk of developing nephropathy Diabetes Care, July 1, 2005; 28(7): 1698 - 1703. [Abstract] [Full Text] [PDF]

				M. C. Thomas, C. Tikellis, P. Kantharidis, W. C. Burns, M. E. Cooper, and J. M. Forbes The Role of Advanced Glycation in Reduced Organic Cation Transport Associated with Experimental Diabetes J. Pharmacol. Exp. Ther., November 1, 2004; 311(2): 456 - 466. [Abstract] [Full Text] [PDF]

				F. Locatelli, B. Canaud, K.-U. Eckardt, P. Stenvinkel, C. Wanner, and C. Zoccali The importance of diabetic nephropathy in current nephrological practice Nephrol. Dial. Transplant., September 1, 2003; 18(9): 1716 - 1725. [Abstract] [Full Text] [PDF]

				D. Koya, K. Hayashi, M. Kitada, A. Kashiwagi, R. Kikkawa, and M. Haneda Effects of Antioxidants in Diabetes-Induced Oxidative Stress in the Glomeruli of Diabetic Rats J. Am. Soc. Nephrol., August 1, 2003; 14(90003): S250 - 253. [Abstract] [Full Text] [PDF]

				E. Cellier, M. Mage, J. Duchene, C. Pecher, R. Couture, J.-L. Bascands, and J.-P. Girolami Bradykinin reduces growth factor-induced glomerular ERK1/2 phosphorylation Am J Physiol Renal Physiol, February 1, 2003; 284(2): F282 - F292. [Abstract] [Full Text] [PDF]

				J. M. Forbes, M. E. Cooper, V. Thallas, W. C. Burns, M. C. Thomas, G. C. Brammar, F. Lee, S. L. Grant, L. A. Burrell, G. Jerums, et al. Reduction of the Accumulation of Advanced Glycation End Products by ACE Inhibition in Experimental Diabetic Nephropathy Diabetes, November 1, 2002; 51(11): 3274 - 3282. [Abstract] [Full Text] [PDF]

				C. S. Shin, B. S. Moon, K. S. Park, S. Y. Kim, S. J. Park, M. H. Chung, and H. K. Lee Serum 8-Hydroxy-Guanine Levels Are Increased in Diabetic Patients Diabetes Care, April 1, 2001; 24(4): 733 - 737. [Abstract] [Full Text]

				A. P. Levy, A. Roguin, I. Hochberg, P. Herer, S. Marsh, F. M. Nakhoul, and K. Skorecki Haptoglobin Phenotype and Vascular Complications in Patients with Diabetes N. Engl. J. Med., September 28, 2000; 343(13): 969 - 970. [Full Text]

				N. TANJI, G. S. MARKOWITZ, C. FU, T. KISLINGER, A. TAGUCHI, M. PISCHETSRIEDER, D. STERN, A. M. SCHMIDT, and V. D. D'AGATI Expression of Advanced Glycation End Products and Their Cellular Receptor RAGE in Diabetic Nephropathy and Nondiabetic Renal Disease J. Am. Soc. Nephrol., September 1, 2000; 11(9): 1656 - 1666. [Abstract] [Full Text]

				T. MIYATA, K. KUROKAWA, and C. VAN YPERSELE DE STRIHOU Advanced Glycation and Lipoxidation End Products: Role of Reactive Carbonyl Compounds Generated during Carbohydrate and Lipid Metabolism J. Am. Soc. Nephrol., September 1, 2000; 11(9): 1744 - 1752. [Full Text]

				V. Scivittaro, M. B. Ganz, and M. F. Weiss AGEs induce oxidative stress and activate protein kinase C-beta II in neonatal mesangial cells Am J Physiol Renal Physiol, April 1, 2000; 278(4): F676 - F683. [Abstract] [Full Text] [PDF]

				D. KOYA, M. HANEDA, H. NAKAGAWA, K. ISSHIKI, H. SATO, S. MAEDA, T. SUGIMOTO, H. YASUDA, A. KASHIWAGI, D. K. WAYS, et al. Amelioration of accelerated diabetic mesangial expansion by treatment with a PKC {beta} inhibitor in diabetic db/db mice, a rodent model for type 2 diabetes FASEB J, March 1, 2000; 14(3): 439 - 447. [Abstract] [Full Text]

				T. MIYATA, S. SUGIYAMA, M. NANGAKU, D. SUZUKI, K.-I. URAGAMI, R. INAGI, H. SAKAI, and K. KUROKAWA Apolipoprotein E2/E5 Variants in Lipoprotein Glomerulopathy Recurred in Transplanted Kidney J. Am. Soc. Nephrol., July 1, 1999; 10(7): 1590 - 1595. [Abstract] [Full Text]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673