scholarly journals 2-Aminoadipic acid is a marker of protein carbonyl oxidation in the aging human skin: effects of diabetes, renal failure and sepsis

2007 ◽  
Vol 404 (2) ◽  
pp. 269-277 ◽  
Author(s):  
David R. Sell ◽  
Christopher M. Strauch ◽  
Wei Shen ◽  
Vincent M. Monnier
Keyword(s):  
Renal Failure ◽  
Human Skin ◽  
Protein Carbonyl ◽  
Catalysed Oxidation ◽  
Skin Collagen ◽  
Lysine Residues ◽  
Selective Ion Monitoring ◽  
Carboxymethyl Lysine ◽  
Reliable Marker ◽  
Age Range

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 (P<0.0001), but not 6-hydroxynorleucine (P=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 (P<0.0001) increased 2-aminoadipic acid up to <3 mmol/mol, but not 6-hydroxynorleucine (levels<0.4 mmol/mol, P=0.18). Renal failure even in the absence of diabetes markedly increased levels reaching up to <0.5 and 8 mmol/mol for 6-hydroxynorleucine and 2-aminoadipic acid respectively. Septicaemia significantly (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.

Age-dependent accumulation of N.epsilon.-(carboxymethyl)lysine and N.epsilon.-(carboxymethyl)hydroxylysine in human skin collagen

Biochemistry ◽  
1991 ◽  
Vol 30 (5) ◽  
pp. 1205-1210 ◽  
Author(s):  
John A. Dunn ◽  
David R. McCance ◽  
Suzanne R. Thorpe ◽  
Timothy J. Lyons ◽  
John W. Baynes
Keyword(s):  
Human Skin ◽  
Skin Collagen ◽  
Age Dependent ◽  
Carboxymethyl Lysine

Aging, Diabetes, and Renal Failure Catalyze the Oxidation of Lysyl Residues to 2-Aminoadipic Acid in Human Skin Collagen

2008 ◽  
Vol 1126 (1) ◽  
pp. 205-209 ◽  
Author(s):  
David R. Sell ◽  
Christopher M. Strauch ◽  
Wei Shen ◽  
Vincent M. Monnier
Keyword(s):  
Renal Failure ◽  
Human Skin ◽  
Skin Collagen

Analysis of the age-related composition of human skin collagen and collagens synthesized by fibroblast culture

1994 ◽  
Vol 286 (7) ◽  
pp. 391-395 ◽  
Author(s):  
J. Brinckmann ◽  
M. Bodo ◽  
M. Brey ◽  
H. H. Wolff ◽  
P. K. M�ller
Keyword(s):  
Human Skin ◽  
Fibroblast Culture ◽  
Age Related ◽  
Skin Collagen

scholarly journals N ε-(Carboxyethyl)lysine, a product of the chemical modification of proteins by methylglyoxal, increases with age in human lens proteins

1997 ◽  
Vol 324 (2) ◽  
pp. 565-570 ◽  
Author(s):  
Mahtab U. AHMED ◽  
Elisabeth BRINKMANN FRYE ◽  
Thorsten P. DEGENHARDT ◽  
Suzanne R. THORPE ◽  
John W. BAYNES
Keyword(s):  
Advanced Glycation End Products ◽  
Human Lens ◽  
Advanced Glycation ◽  
Model Compounds ◽  
Lens Proteins ◽  
Glycation End Products ◽  
End Products ◽  
Lysine Residues ◽  
Carboxymethyl Lysine ◽  
Chemical Modification Of Proteins

Advanced glycation end-products and glycoxidation products, such as Nϵ-(carboxymethyl)lysine (CML) and pentosidine, accumulate in long-lived tissue proteins with age and are implicated in the aging of tissue proteins and in the development of pathology in diabetes, atherosclerosis and other diseases. In this paper we describe a new advanced glycation end-product, Nϵ-(carboxyethyl)lysine (CEL), which is formed during the reaction of methylglyoxal with lysine residues in model compounds and in the proteins RNase and collagen. CEL was also detected in human lens proteins at a concentration similar to that of CML, and increased with age in parallel with the concentration of CML. Although CEL was formed in highest yields during the reaction of methylglyoxal and triose phosphates with lysine and protein, it was also formed in reactions of pentoses, ascorbate and other sugars with lysine and RNase. We propose that levels of CML and CEL and their ratio to one another in tissue proteins and in urine will provide an index of glyoxal and methylglyoxal concentrations in tissues, alterations in glutathione homoeostasis and dicarbonyl metabolism in disease, and sources of advanced glycation end-products in tissue proteins in aging and disease.

Oxidative Damage in the Liver of Rats Treated With Glycolaldehyde

2011 ◽  
Vol 30 (2) ◽  
pp. 253-258 ◽  
Author(s):  
Rodrigo Lorenzi ◽  
Michael Everton Andrades ◽  
Rafael Calixto Bortolin ◽  
Ryoji Nagai ◽  
Felipe Dal-Pizzol ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Failure ◽  
Protein Function ◽  
Liver Diseases ◽  
Protein Carbonyl ◽  
Antioxidant Defenses ◽  
Stress Markers ◽  
Glycation End Products ◽  
Carboxymethyl Lysine

Liver diseases are often associated with hyperglycemia, inflammation, and oxidative stress. These conditions, commonly associated with diabetes mellitus and obesity, facilitate the formation of advanced glycation end products (AGEs). These products are known to impair protein function and promote inflammation. Accumulation of AGEs such as Nε-(carboxymethyl)lysine (CML) is related to chronic liver diseases and their severity. Although several reports suggest a crucial role of AGEs in liver failure, there is little investigation on the direct effects of reducing sugars, precursors of AGEs, and on the onset and progression of liver failure. In this work, we investigate the effects of intravenously administrated glycolaldehyde (GA), a short-chain aldehyde, on oxidative parameters in the liver of Wistar rats. Animals received a single injection of GA (10, 50, or 100 mg/kg) and were sacrificed after 6, 12, or 24 hours. Levels of protein carbonyl, lipid peroxidation, and reduced thiol were quantified. The activities of catalase, superoxide dismutase, and glyoxalase I were also assessed. The amount of CML was quantified with specific antibody. There was an increase in oxidative stress markers in the liver of GA-treated rats. Glycolaldehyde induced a decrease in the activities of all enzymes assayed. Also, all tested doses led to an increase in CML content. Our data suggest that GA might play an important role in liver diseases through the impairment of antioxidant defenses and generation of AGEs.

scholarly journals Evaluation of Calcium Regulating Hormones and Some Biochemical Parameters in Growth Hormone Deficient Patients

2020 ◽  
pp. 499-507
Author(s):  
Shaymaa H. Aldabagh ◽  
Makarim Q. Al-Lami ◽  
Abdilkarim Y. Al-Samarriae
Keyword(s):  
Growth Hormone ◽  
Vitamin D ◽  
Healthy Subjects ◽  
Biochemical Parameters ◽  
Gh Deficiency ◽  
Normal Weight ◽  
Control Group ◽  
The Difference ◽  
Reliable Marker ◽  
Age Range

The present study aims to evaluate levels of calcium regulating hormones and some biochemical parameters in a sample of growth hormone (GH) deficient patients. Seventy five GH deficient patients and twenty healthy subjects used as a control group have been involved in this study during their attendance at the National Diabetic Centerfor Treatment and Research /Al-Mustansiriya University. The studied subjects were in an age range of 3-15 years. Blood samples were collected from the studied subjects to determine levels of basal GH,GH2. and GH3 after 60 mins. and 90mins. of provocation with clonidine. The study also included the measurement of the levels of insulin like growth factor (IGF-1); calcium regulating hormones [parathyroid hormone (PTH) and vitamin D],and some biochemical parameters [calcium (Ca), phosphorus (P), urea, and creatinine].Distribution of the studied groups according to gender revealed that most of the GH deficientpatients (60 %) were males while 40 % were females,with the difference being statistically significant (P<0.05), while the control included two equal subgroups (50 % males and 50 % females). Distribution of the studied groups Distribution of the studied groups Distribution of the studied groups Distribution of the studied groups Distribution of the studied groups Distribution of the studied groups Distribution of the studied groups Distribution of the studied groups Distribution of the studied groups Distribution of the studied groups Distribution of the studied groups Distribution of the studied groups Distribution of the studied groups Distribution of the studied groups Distribution of the studied groups Distribution of the studied groups Distribution of the studied groups Distribution of the studied groups Distribution of the studied groups Distribution of the studied groups Distribution of the studied groups Distribution of the studied groups Distribution of the studied groups Distribution of the studied groups Distribution of the studied groups Distribution of the studied groups according to BMI values showed according to BMI values showed according to BMI values showed according to BMI values showed according to BMI values showed according to BMI values showed according to BMI values showed according to BMI values showed according to BMI values showed according to BMI values showed according to BMI values showed according to BMI values showed according to BMI values showed according to BMI values showed according to BMI values showed according to BMI values showed according to BMI values showed according to BMI values showed according to BMI values showed according to BMI values showed according to BMI values showed according to BMI values showed according to BMI values showed according to BMI values showed that the percentage of underweight was significantly (P<0.01) higher in the patients (48%) compared to the control (10%), while the percentage of normal weight was significantly (P<0.01) higher in the control (85%) as compared to the patients (40%).The results showed highly significant decreases (P<0.01) in the levels of basal GH, GH2 and GH3 in the patients as compared to the control group. Also, IGF-1 levels showed a high significant (P<0.01) decrease in the patients as compared to the control group.The findings of calcium regulating hormones revealed non-significant differences in the levels of PTH and vitamin D between the patients and the control group. Also, the results of the biochemical parameters (Ca, P, urea, and creatinine) showed non-significant differences in their values between the patients and the control group.It can be concluded from the present study that GH deficiency (GHD) seems to be dominating in the males under weighted patients. The diagnosis of GHD cannot be achieved at the basal GH level.IGF-1 is a reliable marker of GH functions. Finally, levels of calcium regulating hormones are not affected by GHD.

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