Glycosylation accelerates albumin degradation in normal and diabetic dogs

doi:10.1016/0885-4505(86)90082-4

Biochemical Medicine and Metabolic Biology

Volume 35, Issue 3, June 1986, Pages 267-270

Biochemical Medicine...

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Abstract

Nonenzymatic glycosylation of albumin was associated with an increased catabolic rate and decreased protein half-life in both normal and diabetic animals. The fractional catabolic rate of glycosylated albumin was increased significantly over albumin, from 0.100 ± 0.004/day to 0.131 ± 0.007/day in normal animals and from 0.104 ± 0.004/day to 0.138 ± 0.007/day when these animals were made diabetic with alloxan. The half-lives of Alb and GlyAlb in normal dogs were 6.81 ± 0.12 days and 4.97 ± 0.21 days, respectively. In diabetic animals, the half-lives of Alb and GlyAlb were 7.48 ± 0.21 and 5.21 ± 0.24 days, respectively. The increased catabolism of GlyAlb may reflect chronic increased extravasation of glycosylated plasma proteins, which are known to be increased in diabetes, into the microvascular wall.

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Variations in native protein glycation and plasma antioxidants in several birds of prey
2017, Comparative Biochemistry and Physiology Part - B: Biochemistry and Molecular Biology
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In fact, values were similar to what has been reported in non-diabetic humans. Species variation in albumin glycation may be due to differences in albumin turnover rates; some research has shown that glycated albumin is more quickly degraded than unmodified albumin in rabbits and dogs (Kallner, 1990; Morris and Preddy, 1986). Alternatively, it is possible that the albumin protein may be folded differently in red-tailed hawks thus potentially shielding lysine residues from glycation or that red-tailed hawks have fewer lysine residues available for glycation.
Birds are an anomaly among vertebrates as they are remarkably long-lived despite having naturally high blood glucose and metabolic rates. For mammals, hyperglycemia leads to oxidative stress and protein glycation. In contrast, many studies have shown that domestic and wild birds are relatively resistant to these glucose-mediated pathologies. Surprisingly very little research has examined protein glycation in birds of prey, which by nature consume a diet high in protein and fat that promotes gluconeogenesis. The purpose of this study was to evaluate protein glycation and antioxidant concentrations in serum samples from several birds of prey (bald eagle (BAEA), red-tailed hawk (RTHA), barred owl (BAOW), great horned owl (GHOW)) as protein glycation can accelerate oxidative stress and vice versa. Serum glucose was measured using a commercially available assay, native albumin glycation was measured by mass spectrometry and various antioxidants (uric acid, vitamin E, retinol and several carotenoids) were measured by high performance liquid chromatography. Although glucose concentrations were not significantly different between species (p = 0.340), albumin glycation was significantly higher (p = 0.004) in BAEA (23.67 ± 1.90%) and BAOW (24.28 ± 1.43%) compared to RTHA (14.31 ± 0.63%). Of the antioxidants examined, lutein was significantly higher in BAOW (p = 0.008). BAEA had the highest beta-cryptoxanthin and beta-carotene concentrations (p < 0.005). The high concentrations of antioxidants in these birds of prey relative to other birds likely helps protect from complications that may otherwise arise from having high glucose and protein glycation.
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Aminoguanidine and metformin prevent the reduced rate of HDL-mediated cell cholesterol efflux induced by formation of advanced glycation end products
2006, International Journal of Biochemistry and Cell Biology
The mechanisms whereby advanced glycation end products (AGE) contribute to atherogenesis in diabetes mellitus are not fully understood. In this study we analyzed in vitro the influence of advanced glycated albumin (AGE-albumin) as well as the role of the AGE inhibitors – aminoguanidine (AMG) and metformin (MF) – on the cell cholesterol efflux.
HDL₃ and albumin-mediated cholesterol efflux was measured in mouse peritoneal macrophages and in SR-BI transfected cells that had been treated along time with dicarbonyl sugars or AGE-albumin, both in the presence or in the absence of AMG and MF. ¹²⁵I-HDL₃ cell binding and ¹²⁵I-AGE-albumin cell degradation were measured. Carboxymethyllysine (CML) formation and SR-BI expressions were determined by immunoblot.
AGE-albumin efficiently trapped cell cholesterol but impaired the HDL-mediated cell cholesterol efflux by decreasing HDL binding to the cell surface and inducing intracellular glycoxidation, without interfering with the SR-BI expression. Cell treatment with dicarbonyl sugars also disrupted the HDL-mediated cell cholesterol efflux, but this was prevented by AMG and MF that reduced CML formation.
By adversely impairing the HDL-mediated cell cholesterol removal rate, AGE-albumin and cell glycoxidation could facilitate the development of premature atherosclerosis in diabetes mellitus (DM) and in other diseases associated with carbonyl and oxidative stress like in chronic uremia. Thus, drugs that prevent AGE formation may be useful to correct disturbances in cell cholesterol transport.
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Background.Delta-bilirubin is a bilirubin covalently bound with albumin, which is nontoxic and excreted neither in urine nor in bile. We previously reported that the percentage of delta-bilirubin increased after biliary drainage and that the rapidly excretable bilirubin fraction (total minus delta-bilirubin) was a better parameter to predict the effectiveness of biliary decompression in the dog model. The aim of the present study was to elucidate whether it is applicable to humans.
Materials and Methods.The serum bilirubin concentration was measured and its fractions were analyzed by high-performance liquid chromatography in 22 patients with obstructive jaundice before and after biliary drainage. In addition, the patients were subgrouped into good and poor drainage groups according to the decline index of serum bilirubin to examine the significance of delta-bilirubin.
Results.The concentration of total bilirubin decreased from 14.1 mg/dl before biliary drainage to 5.4 mg/dl 28 days after drainage. During this period, the percentage of conjugated bilirubin steeply declined from 47.1 to 8.8% and that of excretable bilirubin from 63.4 to 28.6%. In contrast, the proportion of serum delta-bilirubin increased from 36.6 to 71.4%. There was an inverse correlation between percentage of delta-bilirubin and total bilirubin concentration (r= −0.69,P< 0.01). In the good drainage group, the percentage of delta-bilirubin increased above 60% within 7 days after biliary drainage, but it did not reach 60% by 28 days in the poor drainage group. A decreasing rate of total bilirubin minus delta-bilirubin, the excretable bilirubin fraction, was a better index than that of total bilirubin to assess the efficacy of biliary drainage (P< 0.01).
Conclusions.The increase in the percentage of serum delta-bilirubin indicates an effectiveness of biliary drainage in man. An analysis of serum delta-bilirubin for 7 days can distinguish the good drainage patients from the poor drainage patients.
Significance of serum delta bilirubin during obstructive jaundice in dogs
1996, Journal of Surgical Research
Background: δ-Bilirubin, a nonenzymatic covalently bound complex with albumin, is nonenzymatically formed in serum and has a long half-life irrespective of hepatorenal function. The aim was to examine if δ-bilirubin reflects the duration of obstructive jaundice and efficacy of biliary drainage. Materials and methods: Obstructive jaundice was developed in 17 dogs either for 4 (short term;n= 9) or 11 (long term;n= 8) days and then external biliary drainage was performed. Serum total, direct, and δ-bilirubin fractions were analyzed by high-performance liquid chromatography. Results: δ-Bilirubin was not detectable in serum before biliary obstruction. The serum total and direct bilirubin levels increased rapidly and reached a plateau within 2 days after the biliary obstruction, whereas the concentration and proportion of δ-bilirubin gradually increased and significantly correlated with the duration of obstructive jaundice. Before biliary drainage, the proportion of δ-bilirubin was 28.9 ± 2.4% in the short-term and 42.5 ± 2.4% in the long-term obstruction group. The decline indices of serum total, direct, and total minus δ-bilirubin in the short-term group (−0.17, −0.19, and −0.26, respectively) were significantly (P< 0.05) greater than those in the long-term obstruction group (−0.10, −0.10, and −0.13). The decline index of δ-bilirubin itself was similar between the groups. Conclusions: The concentration and proportion of δ-bilirubin in serum reflect the duration of jaundice. Because δ-bilirubin is not excreted into bile and urine and is not toxic to organs, a decline index of total bilirubin minus δ-bilirubin, the excretable bilirubin fraction might be better to assess the efficacy of biliary drainage.

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Glycosylation accelerates albumin degradation in normal and diabetic dogs

Abstract

Arch. Biochem. Biophys.

J. Biol. Chem.

FEBS Lett.

J. Biol. Chem.

Diabetes

J. Clin. Invest.