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Immunohistochemical evidence for an increased oxidative stress and carbonyl modification of proteins in diabetic glomerular lesions.
J Am Soc Nephrol 1999; 10(4):822-32JA

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").

Authors+Show Affiliations

Molecular and Cellular Nephrology, Institute of Medical Sciences, Tokai University School of Medicine, Isehara, 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 availableNo affiliation info available

Pub Type(s)

Clinical Trial
Comparative Study
Controlled Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10203367

Citation

Suzuki, D, et al. "Immunohistochemical Evidence for an Increased Oxidative Stress and Carbonyl Modification of Proteins in Diabetic Glomerular Lesions." Journal of the American Society of Nephrology : JASN, vol. 10, no. 4, 1999, pp. 822-32.
Suzuki D, Miyata T, Saotome N, et al. Immunohistochemical evidence for an increased oxidative stress and carbonyl modification of proteins in diabetic glomerular lesions. J Am Soc Nephrol. 1999;10(4):822-32.
Suzuki, D., Miyata, T., Saotome, N., Horie, K., Inagi, R., Yasuda, Y., ... Kurokawa, K. (1999). Immunohistochemical evidence for an increased oxidative stress and carbonyl modification of proteins in diabetic glomerular lesions. Journal of the American Society of Nephrology : JASN, 10(4), pp. 822-32.
Suzuki D, et al. Immunohistochemical Evidence for an Increased Oxidative Stress and Carbonyl Modification of Proteins in Diabetic Glomerular Lesions. J Am Soc Nephrol. 1999;10(4):822-32. PubMed PMID: 10203367.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immunohistochemical evidence for an increased oxidative stress and carbonyl modification of proteins in diabetic glomerular lesions. AU - Suzuki,D, AU - Miyata,T, AU - Saotome,N, AU - Horie,K, AU - Inagi,R, AU - Yasuda,Y, AU - Uchida,K, AU - Izuhara,Y, AU - Yagame,M, AU - Sakai,H, AU - Kurokawa,K, PY - 1999/4/15/pubmed PY - 1999/4/15/medline PY - 1999/4/15/entrez SP - 822 EP - 32 JF - Journal of the American Society of Nephrology : JASN JO - J. Am. Soc. Nephrol. VL - 10 IS - 4 N2 - 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"). SN - 1046-6673 UR - https://www.unboundmedicine.com/medline/citation/10203367/Immunohistochemical_evidence_for_an_increased_oxidative_stress_and_carbonyl_modification_of_proteins_in_diabetic_glomerular_lesions_ L2 - http://jasn.asnjournals.org/cgi/pmidlookup?view=long&pmid=10203367 DB - PRIME DP - Unbound Medicine ER -