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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.
Open accessAbstract
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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“Excessive AGE formation is particularly associated with cross-linking of matrix proteins such as collagen, vitronectin, and laminin.[2,10,11]”
From The Role of Dietary Advanced Glycation End Products in Metabolic Dysfunction (2021) · cites this paper as [2]
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“The rate of AGE formation in the body is greatly enhanced in diabetes.[2,3]”
From The Role of Dietary Advanced Glycation End Products in Metabolic Dysfunction (2021) · cites this paper as [2]
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Metadata
- 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)
- Venue
- Journal of Clinical Investigation
- Published
- 1997-12-15
- Volume
- 100
- Issue
- 12
- Pages
- 2995-3004
- ISSN
- 0021-9738 (ISSN-L)
- 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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