Measurement of Nε-(Carboxymethyl)lysine and Nε-(Carboxyethyl)lysine in Human Plasma Protein by Stable-Isotope-Dilution Tandem Mass Spectrometry

Teerlink, Tom; Barto, Rob; Brink, H.J. ten; Schalkwijk, Casper G.

doi:10.1373/clinchem.2004.031286

Cited by 117 publications

(108 citation statements)

References 24 publications

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“…In 3T3‐L1 cells treated with CML starting at differentiation, we observed an increase in lipid accumulation to similar extent after treatment with 5, 50, or 500 μM CML. This demonstrates CML to influence lipid accumulation also in plasma relevant concentrations, as plasma concentrations of healthy individuals centre around 2.8 μM [Teerlink et al, 2004], reaching around 12 μM in diabetic subjects with compromised renal function [Lieuw et al, 2004]. Furthermore, trapping of CML in adipose tissue has been reported [Jia et al, 2012], which may yield in even higher local concentrations.…”

Section: Discussionmentioning

confidence: 99%

N^ϵ‐Carboxymethyllysine Increases the Expression of miR‐103/143 and Enhances Lipid Accumulation in 3T3‐L1 Cells

Holik

Lieder

Kretschy

et al. 2016

J of Cellular Biochemistry

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Advanced glycation endproducts, formed in vivo, but also by the Maillard reaction upon thermal treatment of foods, have been associated with the progression of pathological conditions such as diabetes mellitus. In addition to the accumulation with age, exogenous AGEs are introduced into the circulation from dietary sources. In this study, we investigated the effects of addition of free Nϵ‐carboxymethyllysine (CML), a well‐characterized product of the Maillard reaction, on adipogenesis in 3T3‐L1 preadipocytes. Treatment with 5, 50, or 500 μM CML resulted in increased lipid accumulation to similar extents, by 11.5 ± 12.6%, 12.9 ± 8.6%, and 12.8 ± 8.5%, respectively. Long‐term treatment with 500 μM CML during adipogenesis resulted in increases in miR‐103 and miR‐143 levels, two miRNAs described to be involved in impaired glucose homeostasis and increased lipid accumulation. Furthermore, the expression of genes associated with these miRNAs, consisting of Akt1, PI3k, and Cav1 was regulated by CML. Short‐term treatment of mature 3T3‐L1 adipocytes with CML resulted in decreased basal glucose uptake. These results, indicate that the addition of protein‐free CML to 3T3‐L1 cells influence parameters associated with adipogenesis and glucose homeostasis at transcriptional, and functional level; this indicates that free CML derived from exogenous sources, in addition to protein‐bound CML may be relevant in this context. J. Cell. Biochem. 117: 2413–2422, 2016. © 2016 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

N^ϵ‐Carboxymethyllysine Increases the Expression of miR‐103/143 and Enhances Lipid Accumulation in 3T3‐L1 Cells

Holik

Lieder

Kretschy

et al. 2016

J of Cellular Biochemistry

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“…Unbound CML and CEL were measured in EDTA plasma by high-performance liquid chromatography with stable isotope dilution tandem mass spectrometric detection using a procedure developed for the analysis of protein-bound CML and CEL (22), with a modified sample preparation procedure. Briefly, after centrifugation of the plasma samples (5 min at 20,000g), 50 l of the supernatant was mixed with 150 l of a combined internal standard solution (containing deuterated CML and CEL), and proteins were removed by centrifugation (20 min at 15,000g) in a 10-kDa cutoff ultrafiltration device (Vivaspin 500 PES; Vivascience, Hannover, Germany).…”

Section: Laboratory Analysismentioning

confidence: 99%

“…Briefly, after centrifugation of the plasma samples (5 min at 20,000g), 50 l of the supernatant was mixed with 150 l of a combined internal standard solution (containing deuterated CML and CEL), and proteins were removed by centrifugation (20 min at 15,000g) in a 10-kDa cutoff ultrafiltration device (Vivaspin 500 PES; Vivascience, Hannover, Germany). A 90-l aliquot of the ultrafiltrate was mixed with 10 l of a 50 mmol/l nonafluoropentanoic acid solution, and 25 l of this mixture was subjected to liquid chromatography tandem mass spectrometry analysis, as described before (22). Intra-assay and interassay CVs for CML were 3 and 4%, respectively, and for CEL, 5 and 9%, respectively.…”

Section: Laboratory Analysismentioning

confidence: 99%

“…Some studies have shown that total serum CML is higher in type 2 diabetes than in healthy individuals (32,33), although in other studies, no difference was observed (22). We chose not to measure total CML and CEL but rather the unbound forms of these compounds that are continuously released during degradation of intracellular proteins with a rapid turnover.…”

Section: Figure 2-relations Between Postprandial Changes Of the Oxidimentioning

confidence: 99%

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Fasting and Postprandial Glycoxidative and Lipoxidative Stress Are Increased in Women With Type 2 Diabetes

Schindhelm¹,

Alssema

Scheffer

et al. 2007

Diabetes Care

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OBJECTIVE -We studied acute changes in markers of glycoxidative and lipoxidative stress, including oxidized LDL, N ε -(carboxyethyl)-lysine (CEL), N ε -(carboxymethyl)-lysine (CML), and 3-deoxyglucosone (3DG), following two consecutive meals. RESEARCH DESIGN AND METHODS -Postmenopausal women (27 with normal glucose metabolism [NGM], 26 with type 2 diabetes) received two consecutive fat-rich meals and two consecutive carbohydrate-rich meals on two occasions. Glucose and triglyceride concentrations were measured at baseline and 1, 2, 4, 6, and 8 h following breakfast; lunch was given at 4 h. Oxidized LDL-to-LDL cholesterol ratio, CEL, CML, and 3DG were measured at baseline and at 8 h.RESULTS -Fasting oxidized LDL-to-LDL cholesterol ratio, 3DG, and CML were higher in women with type 2 diabetes compared with women with NGM and were comparable to the postprandial values at 8 h in NGM. Postprandial rises in the oxidized LDL-to-LDL cholesterol ratio and 3DG were similar in both groups. However, the oxidized LDL-to-LDL cholesterol ratio increased more after the fat-rich meals, whereas CML and 3DG increased more after the carbohydrate-rich meals. After the fat-rich meals, the increase in the oxidized LDL-to-LDL cholesterol ratio correlated with postprandial triglycerides, whereas the increase in 3DG was correlated with postprandial glucose.CONCLUSIONS -The acute changes in markers of glycoxidative and lipoxidative stress in both type 2 diabetes and NGM suggest that postabsorptive oxidative stress may partly underlie the association of postprandial derangements and cardiovascular risk. Diabetes Care 30:1789-1794, 2007P atients with type 2 diabetes have an increased risk of cardiovascular disease (CVD) (1), which can only partly be explained by classical CVD risk factors such as hypertension, high LDL cholesterol, low HDL cholesterol, and smoking (2). In postmenopausal women compared with men, the relative risk of CVD conferred by type 2 diabetes is even higher (3). Zilversmit (4) postulated in 1979 that disturbances in postprandial metabolism may contribute to the excess risk of CVD due to postprandial elevations of glucose and triglyceride-enriched lipoproteins (5,6).Oxidative stress is regarded as a common pathway by which many of the classical CVD risk factors and postprandial dysmetabolism may initiate and promote atherosclerosis (7). Indeed, elevated levels of oxidized LDL are associated with an increased risk for CVD (8). Prolonged exposure to a high-fat diet has been shown to result in an increase in plasma levels of oxidized LDL (9). Another mechanism that might link postprandial dysmetabolism and the risk of CVD in patients with type 2 diabetes includes the formation of advanced glycation end products (AGEs), which are related to micro-and macrovascular complications (10). Two of the most studied AGEs, N ε -(carboxyethyl)lysine (CEL) and N ε -(carboxymethyl)lysine (CML), can be formed on proteins by both glycoxidation and lipid peroxidation pathways. ␣-Dicarbonyl compounds such as 3-deoxyglucosone (3DG), glyoxal,...

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“…Thus, to assess the degree of glycation at a given pathophysiological condition, precise identification of glycation becomes critical. In this regard, a stable-isotope-dilution tandem mass spectrometry method was employed for simultaneous analysis of CML and CEL in hydrolysates of plasma proteins (28), and 13 C6-glucose was utilized to quantify glycated proteins in the plasma and erythrocytes (29,30). In a recent study, the glycationsensitive peptides of HSA that could serve as markers for early diagnosis of type 2 diabetes were quantified by using an MS-based 18 O-labeling technique (31).…”

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confidence: 99%

Development of Diagnostic Fragment Ion Library for Glycated Peptides of Human Serum Albumin: Targeted Quantification in Prediabetic, Diabetic, and Microalbuminuria Plasma by Parallel Reaction Monitoring, SWATH, and MSE

Korwar

Vannuruswamy

Jagadeeshaprasad

et al. 2015

Molecular & Cellular Proteomics

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Human serum albumin is one of the most abundant plasma proteins that readily undergoes glycation, thus glycated albumin has been suggested as an additional marker for monitoring glycemic status. Hitherto, only Amadori-modified peptides of albumin were quantified. In this study, we report the construction of fragment ion library for Amadori-modified lysine (AML), N()-(carboxymethyl)lysine (CML)-, and N()-(carboxyethyl)lysine (CEL)-modified peptides of the corresponding synthetically modified albumin using high resolution accurate mass spectrometry (HR/AM). The glycated peptides were manually inspected and validated for their modification. Further, the fragment ion library was used for quantification of glycated peptides of albumin in the context of diabetes. Targeted Sequential Window Acquisition of all THeoretical Mass Spectra (SWATH) analysis in pooled plasma samples of control, prediabetes, diabetes, and microalbuminuria, has led to identification and quantification of 13 glycated peptides comprised of four AML, seven CML, and two CEL modifications, representing nine lysine sites of albumin. Five lysine sites namely K549, K438, K490, K88, and K375, were observed to be highly sensitive for glycation modification as their respective m/z showed maximum fold change and had both AML and CML modifications. Thus, peptides involving these lysine sites could be potential novel markers to assess the degree of glycation in diabetes. Molecular & Cellular Proteomics

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Measurement of Nε-(Carboxymethyl)lysine and Nε-(Carboxyethyl)lysine in Human Plasma Protein by Stable-Isotope-Dilution Tandem Mass Spectrometry

Cited by 117 publications

References 24 publications

N^ϵ‐Carboxymethyllysine Increases the Expression of miR‐103/143 and Enhances Lipid Accumulation in 3T3‐L1 Cells

N^ϵ‐Carboxymethyllysine Increases the Expression of miR‐103/143 and Enhances Lipid Accumulation in 3T3‐L1 Cells

Fasting and Postprandial Glycoxidative and Lipoxidative Stress Are Increased in Women With Type 2 Diabetes

Development of Diagnostic Fragment Ion Library for Glycated Peptides of Human Serum Albumin: Targeted Quantification in Prediabetic, Diabetic, and Microalbuminuria Plasma by Parallel Reaction Monitoring, SWATH, and MSE

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Measurement of Nε-(Carboxymethyl)lysine and Nε-(Carboxyethyl)lysine in Human Plasma Protein by Stable-Isotope-Dilution Tandem Mass Spectrometry

Cited by 117 publications

References 24 publications

Nϵ‐Carboxymethyllysine Increases the Expression of miR‐103/143 and Enhances Lipid Accumulation in 3T3‐L1 Cells

Nϵ‐Carboxymethyllysine Increases the Expression of miR‐103/143 and Enhances Lipid Accumulation in 3T3‐L1 Cells

Fasting and Postprandial Glycoxidative and Lipoxidative Stress Are Increased in Women With Type 2 Diabetes

Development of Diagnostic Fragment Ion Library for Glycated Peptides of Human Serum Albumin: Targeted Quantification in Prediabetic, Diabetic, and Microalbuminuria Plasma by Parallel Reaction Monitoring, SWATH, and MSE

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Resources

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N^ϵ‐Carboxymethyllysine Increases the Expression of miR‐103/143 and Enhances Lipid Accumulation in 3T3‐L1 Cells

N^ϵ‐Carboxymethyllysine Increases the Expression of miR‐103/143 and Enhances Lipid Accumulation in 3T3‐L1 Cells