Cited by 433Advanced Glycation End Products researchChronic Kidney Disease and DiabetesRenal Diseases and Glomerulopathies

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Immunohistochemical colocalization of glycoxidation products and lipid peroxidation products in diabetic renal glomerular lesions. Implication for glycoxidative stress in the pathogenesis of diabetic nephropathy.

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Horie, K, Miyata, T, Maeda, K, Miyata, S, Sugiyama, S, Sakai, H, van Ypersole de Strihou, C, Monnier, V M, Witztum, J L, Kurokawa, K·1997·Journal of Clinical Investigation

DOI 10.1172/jci119853PMC PMC508511

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Abstract

Advanced glycation end products (AGEs) include a variety of protein adducts whose accumulation alters the structure and function of tissue proteins and stimulates cellular responses. They have been implicated in tissue damage associated with diabetic complications. To assess the possible link between AGE accumulation and the development of diabetic nephropathy (DN), we have examined the immunohistochemical localization of various AGE structures postulated to date, i.e., pentosidine, Nepsilon-(carboxymethyl)lysine (CML), and pyrraline, in diabetic and control kidneys. CML and pentosidine accumulate in the expanded mesangial matrix and thickened glomerular capillary walls of early DN and in nodular lesions and arterial walls of advanced DN, but were absent in control kidneys. By contrast, pyrraline was not found within diabetic glomeruli but was detected in the interstitial connective tissue of both normal and diabetic kidneys. Although the distribution of pyrraline was topographically identical to type III collagen, distribution of pentosidine and CML was not specific for collagen type, suggesting that difference in matrix protein composition per se could not explain heterogeneous AGE localization. Since oxidation is linked closely to the formation of pentosidine and CML, we also immunostained malondialdehyde (MDA), a lipid peroxidation product whose formation is accelerated by oxidative stress, assuming that local oxidative stress may serve as a mechanism of pentosidine and CML accumulation. Consistent with our assumption, diabetic nodular lesions were stained positive for MDA. These findings show that AGE localization in DN varies according to AGE structure, and suggest that the colocalization of markers of glycoxidation (pentosidine and CML) with a marker of lipid peroxidation reflects a local oxidative stress in association with the pathogenesis of diabetic glomerular lesions. Thus, glycoxidation markers may serve as useful biomarkers of oxidative damage in DN.

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High levels of oxidized LDL in circulating immune complexes are associated with increased odds of developing abnormal albuminuria in Type 1 diabetes
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Background
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Background
Redox-Linked Cell Surface-Oriented Signaling for T-Cell Death
Akhand, A. A., Du, J., Liu, W., Hossain, K., Miyata, T., Nagase, F., Kato, M., Suzuki, H., & Nakashima, I. (2002) · Antioxidants and Redox Signaling · doi:10.1089/15230860260196236 · Cited by 37
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Self-citation
Renoprotective Effect of Breviscapine through Suppression of Renal Macrophage Recruitment in Streptozotocin-Induced Diabetic Rats
Qi, X. M., Wu, G. Z., Wu, Y. G., Lin, H., Shen, J. J., & Shan, L. (2006) · Nephron Experimental Nephrology · doi:10.1159/000094966 · Cited by 36
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Background
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BackgroundMethod
The Potential Role of Advanced Glycation End Products in the Development of Kidney Disease
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“…diseases: AGE staining is observed in the glomeruli of focal segmental glomeru-losclerosis, hypertensive glomerulosclerosis, and lupus nephritis, with the deeper staining of AGEs seen in damaged glomeruli (such as sclerosing glomeruli, nodular lesions, and ischemic crescent formations) [103,104].”
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BackgroundMethodInfluentialSelf-citation
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Background
[11] Advanced glycation end products: Detection and reversal
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“Moreover, the following mechanisms are deemed to be key processes in the formation of intracellular oxidative stress in diabetes: (1) the decrease in the reduced nicotinamide adenine dinucleotide phosphate level, induced by activation of the polyol pathway and/or by the abnormality in the pentose pathway, perturbs sup…”
Background
Evaluation of the Antioxidant and Antiglycation Effects of Lactarius deterrimus and Castanea sativa Extracts on Hepatorenal Injury in Streptozotocin-Induced Diabetic Rats
Јovanović, J. A., Mihailović, M., Uskoković, A. S., Grdović, N., Dinić, S., Poznanović, G., Mujić, I., & Vidaković, M. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00793 · Cited by 31
“Almost all renal structures are susceptible to accumulate AGEs, particularly CML under diabetic conditions (Horie et al., 1997).”
Background
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“As such OxPL were discovered in atherosclerotic lesions [14–16], plasma of patients with coronary artery disease [17], inflamed lung tissue [18–20], diabetic renal glomerulopathy [21], peritoneal dialysate of patients undergoing chronic peritoneal dialysis [7], in hemochromatosis [22], on apoptotic cells [23–25], on c…”
Background
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“However, we favor the explanation that, in our model, the increase in CML can be used as a biomarker for oxidative damage, as has been suggested before (41,42).”
Method
Pharmacogenomic effect of vitamin E on kidney structure and function in transgenic mice with the haptoglobin 2-2 genotype and diabetes mellitus
Nakhoul, F. M., Miller‐Lotan, R., Awad, H., Asleh, R., Jad, K., Nakhoul, N., Asaf, R., Abu‐Saleh, N., & Levy, A. P. (2009) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.90655.2008 · Cited by 28
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“Since lipid peroxidation is significantly elevated in diabetes and end-products of lipid peroxidation are known to accumulate in human diabetes, including the glomeruli [47,48], the implications of our findings may be of clinical relevance in diabetic CKDs.”
Background
Dunaliella salina Attenuates Diabetic Neuropathy Induced by STZ in Rats: Involvement of Thioredoxin
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“CML, one of the more abundant AGE structures identified to date, is a product of glycoxidation (combined nonenzymatic glycation and oxidation) and lipid peroxidation [16–19].”
Background
Skin autofluorescence is associated with progression of kidney disease in type 2 diabetes: A prospective cohort study from the Hong Kong diabetes biobank
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“These complex LF aggregates, similar to other long-life cellular proteins, could be subjected to glycation, probably forming a part of AGE deposits (Horie et al., 1997a, 1997b; Jobst and Lakatos, 1996).”
Background
The Effect of increasing levels of date palm (Phoenix dactylifera L.) seed on the performance, ruminal fermentation, antioxidant status and milk fatty acid profile of Saanen dairy goats
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“As an end product of lipid peroxidation, the formation of MDA is accelerated by oxidative stress (Horie et al., 1997); thus, detection of MDA can reflect the level of oxygen-free radicals and the extent of lipid peroxidation.”
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Dicarbonyl derived post-translational modifications: chemistry bridging biology and aging-related disease
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Background
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Self-citation
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Authors: Horie, K., Miyata, T., Maeda, K., Miyata, S., Sugiyama, S., Sakai, H., van Ypersole de Strihou, C., Monnier, V. M., Witztum, J. L., & Kurokawa, K.
Affiliations: Nagoya University (JP)
Tokai University (JP)
Kobe University (JP)
Chukyo Hospital (JP)
Case Western Reserve University (US)
University of California San Diego (US)
ORCID: Miyata, T
Maeda, K
Miyata, S
Sugiyama, S
Monnier, V M
Kurokawa, K
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1997-12-15
Volume: 100
Issue: 12
Pages: 2995-3004
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci119853
PMC: PMC508511
OpenAlex: W2085341182
Cited by: 433
References: 56
Citations by year: 2026: 3 · 2025: 8 · 2024: 5 · 2023: 7 · 2022: 9 · 2021: 14 · 2020: 10 · 2019: 10 · 2018: 7 · 2017: 12 · 2016: 10 · 2015: 8 · 2014: 14 · 2013: 9 · 2012: 15
FWCI: 14.04
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
DIAL (Catholic University of Leuven) (submittedVersion, other-oa)
Funders: Japan Society for the Promotion of Science (96L00303)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
Keywords: advanced glycation end products, glycoxidation, lipid peroxidation, diabetic nephropathy, pentosidine, carboxymethyllysine, pyrraline, malondialdehyde, oxidative stress, glomerular lesions, mesangial matrix, type III collagen, oxidative damage biomarkers
MeSH terms: Adolescent, Adult, Aged, Animals, Antibodies, Arginine, Collagen, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Female, Humans, Immunoenzyme Techniques, Kidney Glomerulus, Lysine, Male, Malondialdehyde, Middle Aged, Nephrotic Syndrome, Norleucine, Pyrroles, Rabbits, Lipid Peroxidation, Glycation End Products, Advanced, Mice

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Immunohistochemical colocalization of glycoxidation products and lipid peroxidation products in diabetic renal glomerular lesions. Implication for glycoxidative stress in the pathogenesis of diabetic nephropathy.

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