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Site-specific AGE modifications in the extracellular matrix: a role for glyoxal in protein damage in diabetes.

ABSTRACT: Non-enzymatic modification of proteins in hyperglycemia is a major proposed mechanism of diabetic complications. Specifically, advanced glycation end products (AGEs) derived from hyperglycemia-induced reactive carbonyl species (RCS) can have pathogenic consequences when they target functionally critical protein residues. Modification of a small number of these critical residues, often undetectable by the methodologies relying on measurements of total AGE levels, can cause significant functional damage. Therefore, detection of specific sites of protein damage in diabetes is central to understanding the molecular basis of diabetic complications and for identification of biomarkers which are mechanistically linked to the disease. The current paradigm of RCS-derived protein damage places a major focus on methylglyoxal (MGO), an intermediate of cellular glycolysis. We propose that glyoxal (GO) is a major contributor to extracellular matrix (ECM) damage in diabetes. Here, we review the current knowledge and provide new data about GO-derived site-specific ECM modification in experimental diabetes.

SUBMITTER: Voziyan P

PROVIDER: S-EPMC4104777 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Site-specific AGE modifications in the extracellular matrix: a role for glyoxal in protein damage in diabetes.

Voziyan Paul P Brown Kyle L KL Chetyrkin Sergei S Hudson Billy B

Clinical chemistry and laboratory medicine 20140101 1

Non-enzymatic modification of proteins in hyperglycemia is a major proposed mechanism of diabetic complications. Specifically, advanced glycation end products (AGEs) derived from hyperglycemia-induced reactive carbonyl species (RCS) can have pathogenic consequences when they target functionally critical protein residues. Modification of a small number of these critical residues, often undetectable by the methodologies relying on measurements of total AGE levels, can cause significant functional ...[more]

PMID: 23492568

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Site-specific AGE modifications in the extracellular matrix: a role for glyoxal in protein damage in diabetes.

Publications

Site-specific AGE modifications in the extracellular matrix: a role for glyoxal in protein damage in diabetes.

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