2-Aminoadipic acid is a marker of protein carbonyl oxidation in the aging human skin: effects of diabetes, renal failure and sepsis
- 14 May 2007
- journal article
- Published by Portland Press Ltd. in Biochemical Journal
- Vol. 404 (2) , 269-277
- https://doi.org/10.1042/bj20061645
Abstract
We hypothesized that the ϵ-amino group of lysine residues in longlived proteins oxidatively deaminates with age forming the carbonyl compound, allysine (α-aminoadipic acid-δ-semialdehyde), which can further oxidize into 2-aminoadipic acid. In the present study, we measured both products in insoluble human skin collagen from n=117 individuals of age range 10–90 years, of which n=61 and n=56 were non-diabetic and diabetic respectively, and a total of n=61 individuals had either acute or chronic renal failure. Allysine was reduced by borohydride into 6-hydroxynorleucine and both products were measured in acid hydrolysates by selective ion monitoring gas chromatography (GC)-MS. The results showed that 2-aminoadipic acid (PP=0.14), significantly increased with age reaching levels of 1 and 0.3 mmol/mol lysine at late age respectively. Diabetes in the absence of renal failure significantly (PP=0.18). Renal failure even in the absence of diabetes markedly increased levels reaching up to P<0.0001) elevated 2-aminoadipic acid in non-diabetic, but not diabetic individuals, and mildly correlated with other glycoxidation markers, carboxymethyl-lysine and the methylglyoxal-derived products, carboxyethyl-lysine, argpyrimidine and MODIC (methylglyoxal-derived imidazolium cross-link). These results provide support for the presence of metal-catalysed oxidation (the Suyama pathway) in diabetes and the possible activation of myeloperoxidase during sepsis. We conclude that 2-aminoadipic acid is a more reliable marker for protein oxidation than its precursor, allysine. Its mechanism of formation in each of these conditions needs to be elucidated.Keywords
This publication has 48 references indexed in Scilit:
- Bioartificial kidney in the treatment of acute renal failure associated with sepsis (Review Article)Nephrology, 2006
- Myeloperoxidase as a Marker of Hemodialysis Biocompatibility and Oxidative Stress: The Underestimated Modifying Effects of HeparinAmerican Journal of Kidney Diseases, 2006
- Tyrosine Modification Is Not Required for Myeloperoxidase-induced Loss of Apolipoprotein A-I Functional ActivitiesPublished by Elsevier ,2005
- Endotoxemic acute renal failure is attenuated in caspase-1-deficient miceAmerican Journal of Physiology-Renal Physiology, 2005
- The Effect of Ciprofloxacin and Gentamicin on Spinal Morphine-Induced Antinociception in Rats*Basic & Clinical Pharmacology & Toxicology, 2005
- Aging effect on myeloperoxidase in rat kidney and its modulation by calorie restrictionFree Radical Research, 2005
- T Cells Modulate Neutrophil-Dependent Acute Renal Failure during EndotoxemiaJournal of the American Society of Nephrology, 2005
- Conversion of Arginine into Ornithine by Advanced Glycation in Senescent Human Collagen and Lens CrystallinsJournal of Biological Chemistry, 2004
- Proteolysis in Severe Sepsis is Related to Oxidation of Plasma ProteinThe European Journal of Surgery, 2002
- Ageing promotes the increase of early glycation Amadori product as assessed by ϵ-N-(2-furoylmethyl)-l-lysine (furosine) levels in rodent skin collagenMechanisms of Ageing and Development, 1997