Increased accumulation of the glycoxidation product N(epsilon)-(carboxymethyl)lysine in human tissues in diabetes and aging.
Open accessAbstract
N(epsilon)-(Carboxymethyl)lysine (CML), a major product of oxidative modification of glycated proteins, has been suggested to represent a general marker of oxidative stress and long-term damage to proteins in aging, atherosclerosis, and diabetes. To investigate the occurrence and distribution of CML in humans an antiserum specifically recognizing protein-bound CML was generated. The oxidative formation of CML from glycated proteins was reduced by lipoic acid, aminoguanidine, superoxide dismutase, catalase, and particularly vitamin E and desferrioxamine. Immunolocalization of CML in skin, lung, heart, kidney, intestine, intervertebral discs, and particularly in arteries provided evidence for an age-dependent increase in CML accumulation in distinct locations, and acceleration of this process in diabetes. Intense staining of the arterial wall and particularly the elastic membrane was found. High levels of CML modification were observed within atherosclerotic plaques and in foam cells. The preferential location of CML immunoreactivity in lesions may indicate the contribution of glycoxidation to the processes occurring in diabetes and aging. Additionally, we found increased CML content in serum proteins in diabetic patients. The strong dependence of CML formation on oxidative conditions together with the increased occurrence of CML in diabetic serum and tissue proteins suggest a role for CML as endogenous biomarker for oxidative damage.
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The rate of AGE formation in the body is greatly enhanced in diabetes.
“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 [3]
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- Authors
- Schleicher, E. D., Wagner, E., & Nerlich, A. G.
- Affiliations
- University of Tübingen (DE)
- Universitätsklinikum Tübingen (DE)
- ORCID
- Schleicher, E D
- Venue
- Journal of Clinical Investigation
- Published
- 1997-02-01
- Volume
- 99
- Issue
- 3
- Pages
- 457-468
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC507819
- OpenAlex
- W2089878313
- Cited by
- 714
- References
- 45
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 14 · 2023: 17 · 2022: 15 · 2021: 23 · 2020: 24 · 2019: 22 · 2018: 20 · 2017: 26 · 2016: 22 · 2015: 28 · 2014: 35 · 2013: 29 · 2012: 22
- FWCI
- 15.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- carboxymethyllysine, glycoxidation, advanced glycation end products, oxidative stress, diabetes mellitus, aging, atherosclerosis, atherosclerotic plaque, foam cells, arterial wall, serum proteins, alpha-lipoic acid, vitamin E, deferoxamine, superoxide dismutase, catalase, aminoguanidine
- MeSH terms
- Adult, Aged, Aging, Antibodies, Epitopes, Arteries, Arteriosclerosis, Blood Proteins, Catalase, Child, Deferoxamine, Diabetes Mellitus, Enzyme-Linked Immunosorbent Assay, Female, Fetus, Foam Cells, Guanidines, Humans, Immunohistochemistry, Intervertebral Disc, Intestinal Mucosa, Kidney, Thioctic Acid, Lung, Lysine, Middle Aged, Myocardium, Oxidation-Reduction, Pregnancy, Skin, Superoxide Dismutase, Time Factors, Vitamin E, Molecular Structure, Biomarkers, Oxidative Stress
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