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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.
J Clin Invest 1997; 100(12):2995-3004JCI

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.

Authors+Show Affiliations

Department of Internal Medicine, Nagoya University School of Medicine, Nagoya 461, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9399945

Citation

Horie, K, et al. "Immunohistochemical Colocalization of Glycoxidation Products and Lipid Peroxidation Products in Diabetic Renal Glomerular Lesions. Implication for Glycoxidative Stress in the Pathogenesis of Diabetic Nephropathy." The Journal of Clinical Investigation, vol. 100, no. 12, 1997, pp. 2995-3004.
Horie K, Miyata T, Maeda K, et al. Immunohistochemical colocalization of glycoxidation products and lipid peroxidation products in diabetic renal glomerular lesions. Implication for glycoxidative stress in the pathogenesis of diabetic nephropathy. J Clin Invest. 1997;100(12):2995-3004.
Horie, K., Miyata, T., Maeda, K., Miyata, S., Sugiyama, S., Sakai, H., ... Kurokawa, K. (1997). Immunohistochemical colocalization of glycoxidation products and lipid peroxidation products in diabetic renal glomerular lesions. Implication for glycoxidative stress in the pathogenesis of diabetic nephropathy. The Journal of Clinical Investigation, 100(12), pp. 2995-3004.
Horie K, et al. Immunohistochemical Colocalization of Glycoxidation Products and Lipid Peroxidation Products in Diabetic Renal Glomerular Lesions. Implication for Glycoxidative Stress in the Pathogenesis of Diabetic Nephropathy. J Clin Invest. 1997 Dec 15;100(12):2995-3004. PubMed PMID: 9399945.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immunohistochemical colocalization of glycoxidation products and lipid peroxidation products in diabetic renal glomerular lesions. Implication for glycoxidative stress in the pathogenesis of diabetic nephropathy. AU - Horie,K, AU - Miyata,T, AU - Maeda,K, AU - Miyata,S, AU - Sugiyama,S, AU - Sakai,H, AU - van Ypersole de Strihou,C, AU - Monnier,V M, AU - Witztum,J L, AU - Kurokawa,K, PY - 1998/1/31/pubmed PY - 1998/1/31/medline PY - 1998/1/31/entrez SP - 2995 EP - 3004 JF - The Journal of clinical investigation JO - J. Clin. Invest. VL - 100 IS - 12 N2 - 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. SN - 0021-9738 UR - https://www.unboundmedicine.com/medline/citation/9399945/Immunohistochemical_colocalization_of_glycoxidation_products_and_lipid_peroxidation_products_in_diabetic_renal_glomerular_lesions__Implication_for_glycoxidative_stress_in_the_pathogenesis_of_diabetic_nephropathy_ L2 - https://doi.org/10.1172/JCI119853 DB - PRIME DP - Unbound Medicine ER -