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Johan M. Tekoppele - One of the best experts on this subject based on the ideXlab platform.

  • age related accumulation of maillard reaction products in human articular cartilage collagen
    Biochemical Journal, 2000
    Co-Authors: Nicole Verzijl, Esther Oldehinkel, Michael T Bayliss, Johannes W. J. Bijlsma, Jack Degroot, Ruud A Bank, John W. Baynes, Suzanne R. Thorpe, Floris P J G Lafeber, Johan M. Tekoppele
    Abstract:

    Non-enzymic modification of tissue proteins by reducing sugars, the so-called Maillard reaction, is a prominent feature of aging. In articular cartilage, relatively high levels of the advanced glycation end product (AGE) Pentosidine accumulate with age. Higher Pentosidine levels have been associated with a stiffer collagen network in cartilage. However, even in cartilage, Pentosidine levels themselves represent < 1 cross-link per 20 collagen molecules, and as such cannot be expected to contribute sub-stantially to the increase in collagen network stiffness. In the present study, we investigated a broad range of Maillard reaction products in cartilage collagen in order to determine whether Pentosidine serves as an adequate marker for AGE levels. Not only did the well-characterized AGEs Pentosidine, N(e)-(carboxymethyl)lysine, and N(e)-(carboxyethyl)lysine increase with age in cartilage collagen (all P < 0.0001), but also general measures of AGE cross-linking, such as browning and fluorescence (both P < 0.0001), increased. The levels of these AGEs are all higher in cartilage collagen than in skin collagen. As a functional measure of glycation the digestibility of articular collagen by bacterial collagenase was investigated; digestibility decreased linearly with age, proportional to the extent of glycation. Furthermore, the arginine content and the sum of the hydroxylysine and lysine content of cartilage collagen decrease significantly with age (P < 0.0001 and P < 0.01 respectively), possibly due to modification by the Maillard reaction. The observed relationship between glycation and amino acid modification has not been reported previously in vivo. Our present results indicate that extensive accumulation of a variety of Maillard reaction products occurs in cartilage collagen with age. Altogether our results support the hypothesis that glycation contributes to stiffer and more brittle cartilage with advancing age.

  • influence of site and age on biochemical characteristics of the collagen network of equine articular cartilage
    American Journal of Veterinary Research, 1999
    Co-Authors: P A J Brama, Johan M. Tekoppele, Ruud A Bank, P R Van Weeren, A Barneveld
    Abstract:

    Objective - To determine variations in biochemical characteristics of equine articular cartilage in relation to age and the degree of predisposition for osteochondral disease at a specific site. Sample Population - Articular cartilage specimens from 53 horses 4 to 30 years old. Procedure - Healthy specimens were obtained from 2 locations on the proximal articular surface of the first phalanx that had different disease prevalences (site 1 at the mediodorsal margin and site 2 at the center of the medial cavity). Water, total collagen, and hydroxylysine contents and enzymatic (hydroxylysylpyridinoline [HP]) and nonenzymatic (Pentosidine) crosslinking were determined at both sites. Differences between sites were analyzed by ANOVA (factors, site, and age), and age correlation was tested by Pearson's product-moment correlation analysis. Significance was set at P < 0.01. Results - Correlation with age was not found for water, collagen, hydroxylysine contents, and enzymatic cross-linking. Nonenzymatic crosslinking was higher in older horses and was linearly related to age (r = 0.94). Water and collagen contents and HP and Pentosidine crosslinks were significantly higher at site 1. Hydroxylysine content was significantly lower at site 1. Conclusions - Except for nonenzymatic glycation, the composition of articular cartilage collagen does not change significantly in adult horses. A significant topographic variation exists in biochemical characteristics of the articular cartilage collagen network in equine metacarpophalangeal joints. These differences may influence local biomechanical properties and, hence, susceptibility to osteochondral disease, as will greater Pentosidine crosslinks in older horses that are likely to cause stiffer and more brittle cartilage.

  • Age-related decrease in proteoglycan synthesis of human articular chondrocytes: the role of nonenzymatic glycation.
    Arthritis and rheumatism, 1999
    Co-Authors: Jeroen Degroot, Johannes W. J. Bijlsma, Nicole Verzijl, Ruud A Bank, Floris P J G Lafeber, Johan M. Tekoppele
    Abstract:

    Objective. To examine the effect of nonenzymatic glycation of cartilage extracellular matrix on the synthetic activity of chondrocytes. Methods. The proteoglycan-synthesis rate (35SO42- incorporation) and levels of advanced nonenzymatic glycation (determined by high-performance liquid chromatography measurement of Pentosidine) were evaluated in human articular cartilage from 129 donors, varying in age from 25 to 88 years, and in cartilage with enhanced levels of advanced glycation end-products (AGEs) resulting from incubation with ribose. Results. Cartilage showed a strong age-related increase in Pentosidine levels (r = 0.97, P < 0.0005) and, concomitantly, a decrease in proteoglycan synthesis (r = -0.98, P < 0.0002). This decrease in proteoglycan synthesis correlated with the increase in Pentosidine (r = -0.95, P < 0.02). Moreover, the elevation of Pentosidine levels in the in vitro-ribosylated cartilage was proportional with the decrease in proteoglycan synthesis (r = -0.95, P < 0.005). Conclusion. In both aged and in vitro AGE-enriched cartilage, the rate of proteoglycan synthesis was negatively correlated with the degree of glycation. This suggests that the age-related increase in cartilage AGE levels may be responsible, at least in part, for the age-related decline in the synthetic capacity of cartilage.

  • ageing and zonal variation in post translational modification of collagen in normal human articular cartilage the age related increase in non enzymatic glycation affects biomechanical properties of cartilage
    Biochemical Journal, 1998
    Co-Authors: Ruud A Bank, Michael T Bayliss, Floris P J G Lafeber, A Maroudas, Johan M. Tekoppele
    Abstract:

    A biomechanical failure of the collagen network is postulated in many hypotheses of the development of osteoarthritis with advancing age. Here we investigate the accumulation of non-enzymatic glycation (NEG) products in healthy human articular cartilage, its relation to tissue remodelling and its role in tissue stiffening. Pentosidine levels were low up to age 20 years, and increased linearly after this age. This indicates extensive tissue remodelling at young age, and slow turnover of collagen after maturity has been reached. The slow remodelling is supported by the finding that enzymatic modifications of collagen (hydroxylysine, hydroxylysylpyridinoline, and lysylpyridinoline) were not related to age. The high remodelling is supported by levels of the crosslink lysylpyridinoline (LP) as a function of distance from the articular surface. LP was highest at the surface in mature cartilage (> 20 years), whereas in young cartilage (< 10 years) the opposite was seen; highest levels were close to the bone. LP levels in cartilage sections at age 14 years are high at the surface and close to the bone, but they are low in the middle region. This indicates that maturation of cartilage in the second decade of life starts in the upper half of the tissue, and occurs last in the tissue close to the bone. The effect of NEG products on instantaneous deformation of cartilage was investigated as a functional of topographical variations in Pentosidine levels in vivo and in relation to in vitro induced NEG. Consistently, higher Pentosidine levels were associated with a stiffer collagen network. A stiffer and more crosslinked collagen network may become more brittle and more prone to fatigue.

  • sensitive fluorimetric quantitation of pyridinium and Pentosidine crosslinks in biological samples in a single high performance liquid chromatographic run
    Journal of Chromatography B: Biomedical Sciences and Applications, 1997
    Co-Authors: Ruud A Bank, Nicole Verzijl, B Beekman, Jeroen A D M De Roos, Nico A Sakkee, Johan M. Tekoppele
    Abstract:

    A high-performance liquid chromatographic assay was developed for pyridinium crosslinks and Pentosidine in mature collagen of a wide variety of connective tissue hydrolysates by a simple two-step isocratic assay using a reversed-phase column. The crosslinks (including the internal standard pyridoxine) were optimally detected by their native fluorescence by switching wavelengths of the detector during the assay. The method resulted in highly sensitive and accurate measurements, without need for precleaning of the samples: crosslink levels in 200 μm thin slices of the various zones of articular cartilage were easily quantified. The detection limit was as low as 0.4 pmol for the pyridinolines and 0.05 pmol for Pentosidine. The intra- assay and inter-assay coefficients of variation were as low as 2% (pyridinolines) and 5% (Pentosidine); calibration curves for all compounds were linear over a concentration range larger than two orders of magnitude. With our chromatographic system, the diglycosylated form of hydroxylysylpyridinoline in unhydrolyzed urine was separated as well. Chemicals/CAS: Arginine, 74-79-3; Cross-Linking Reagents; Lysine, 56-87-1; Pentosidine, 124505-87-9; Pyridinium Compounds

Toshio Miyata - One of the best experts on this subject based on the ideXlab platform.

  • Increase in the Advanced Glycation End Product Pentosidine in Bruch's Membrane with Age
    2013
    Co-Authors: James T. H, Nicole Verzijl, Toshio Miyata, Gerard A. Lutty, Leonard M. Hjelmel
    Abstract:

    PURPOSE. TO determine whether there is an age-related increase of Pentosidine in human Bruch's membranes and to localize Pentosidine and carboxymethyllysine (CML), two well-characterized, advanced glycation end products (AGEs) in aged human Bruch's membranes and choroid in vivo. METHODS. Human Bruch's membrane samples were isolated from the retinal pigment epithelium (RPE) and choroid and subjected to reversed-phase high-performance liquid chromatography to determine Pentosidine content. A polyclonal anti-Pentosidine antibody and a monoclonal antibody specific for carboxymethyllysine were used to localize AGEs in 20-month-old nondiabetic, 82-year-old nondiabetic, and 82-year-old diabetic globes. RESULTS. Human Bruch's membranes (n = 20) showed a linear age-dependent increase in Pentosidine that reache

  • anti hypertensive agents inhibit in vivo the formation of advanced glycation end products and improve renal damage in a type 2 diabetic nephropathy rat model
    Journal of The American Society of Nephrology, 2003
    Co-Authors: Masaomi Nangaku, Toshio Miyata, Yasuhiko Ueda, Toshio Sada, Makoto Mizuno, Reiko Inagi, Naoyoshi Ishikawa, Hiroko Yuzawa, Hiroyuki Koike, C Van Ypersele De Strihou
    Abstract:

    Prevention or retardation of diabetic nephropathy (DN) includes anti-hypertensive treatment with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB) on the premises that these drugs have an added protective effect beyond their influence on BP. The present study used a strain of spontaneously hypertensive/NIH-corpulent rats [SHR/NDmc-cp (fat/fat)] as a model of type II DN to unravel the renoprotective effects of anti-hypertensive drugs. Olmesartan (1 or 5 mg/kg per d), an ARB, and hydralazine (5 mg/kg per d), an anti-hypertensive drug without effect on the renin-angiotensin system (RAS), were given for 20 wk. BP, renal function, glucose and insulin levels, and proteinuria were monitored. Glomerular lesions and kidney Pentosidine content were assessed at the end of the study. Olmesartan (1 and 5 mg) significantly reduced BP and kidney Pentosidine content and improved histologic renal damage and proteinuria. The changes were dose-dependent. The effect of hydralazine (5 mg) was similar to that of olmesartan (1 mg) but reached statistical significance only for kidney Pentosidine content. The similarity of both drugs' effects on kidney damage and proteinuria suggest that renoprotection does not hinge on manipulation of RAS in these rats. By contrast, the inhibition of renal Pentosidine formation assessed both by immunohistochemistry and HPLC suggests a critical role of advanced glycation end product (AGE) formation together with hypertension in the genesis of diabetic nephropathy. This view is supported by the correlation found between renal Pentosidine content and proteinuria. The unsuspected AGE-lowering, effect of hydralazine was further confirmed in vitro and elucidated; it is due to both reactive carbonyl compounds trapping and modifications of the oxidative metabolism. It is concluded that AGE inhibition should be included in the therapeutic strategy of DN.

  • immunohistochemical evidence for an increased oxidative stress and carbonyl modification of proteins in diabetic glomerular lesions
    Journal of The American Society of Nephrology, 1999
    Co-Authors: Daisuke Suzuki, Katsunori Horie, Toshio Miyata, Yoshinari Yasuda, Reiko Inagi, Noboru Saotome, Koji Uchida, Yuko Izuhara, Mitsunori Yagame, Hideto Sakai
    Abstract:

    Abstract . Advanced glycation end products (AGE) include a variety of protein adducts whose accumulation has been implicated in tissue damage associated with diabetic nephropathy (DN). It was recently demonstrated that among AGE, glycoxidation products, whose formation is closely linked to oxidation, such as carboxymethyllysine (CML) and Pentosidine, accumulate in expanded mesangial matrix and nodular lesions in DN, in colocalization with malondialdehyde-lysine (MDA-lysine), a lipoxidation product, whereas pyrraline, another AGE structure whose deposition is rather independent from oxidative stress, was not found within diabetic glomeruli. Because CML, Pentosidine, and MDA-lysine are all formed under oxidative stress by carbonyl amine chemistry between protein amino group and carbonyl compounds, their colocalization suggests a local oxidative stress and increased protein carbonyl modification in diabetic glomerular lesions. To address this hypothesis, human renal tissues from patients with DN or IgA nephropathy were examined with specific antibodies to characterize most, if not all, carbonyl modifications of proteins by autoxidation products of carbohydrates, lipids, and amino acids: CML (derived from carbohydrates, lipids, and amino acid), Pentosidine (derived from carbohydrates), MDA-lysine (derived from lipids), 4-hydroxynonenal-protein adduct (derived from lipids), and acrolein-protein adduct (derived from lipids and amino acid). All of the protein adducts were identified in expanded mesangial matrix and nodular lesions in DN. In IgA nephropathy, another primary glomerular disease leading to end-stage renal failure, despite positive staining for MDA-lysine and 4-hydroxynonenal-protein adduct in the expanded mesangial area, CML, Pentosidine, and acrolein-protein adduct immunoreactivities were only faint in glomeruli. These data suggest a broad derangement in nonenzymatic biochemistry in diabetic glomerular lesions, and implicate an increased local oxidative stress and carbonyl modification of proteins in diabetic glomerular tissue damage (“carbonyl stress”).

  • accumulation of carbonyls accelerates the formation of Pentosidine an advanced glycation end product carbonyl stress in uremia
    Journal of The American Society of Nephrology, 1998
    Co-Authors: Toshio Miyata, Kiyoshi Kurokawa, Yasuhiko Ueda, Y Yamada, Y Izuhara, Takehiko Wada, Michel Jadoul, Akira Saito, C Van Ypersele De Strihou
    Abstract:

    Advanced glycation end product (AGE) formation is related to hyperglycemia in diabetes but not in uremia, because plasma AGE levels do not differ between diabetic and nondiabetic hemodialysis patients. The mechanism of this phenomenon remains elusive. Previously, it was suggested that elevation of AGE levels in uremia might result from the accumulation of unknown AGE precursors. The present study evaluates the in vitro generation of Pentosidine, a well identified AGE structure. Plasma samples from healthy subjects and nondiabetic hemodialysis patients were incubated under air for several weeks. Pentosidine levels were determined al:intervals by HPLC assay. Pentosidine rose to a much larger extent in uremic than in control plasma. Pentosidine yield, i.e., the change in Pentosidine level between 0 and 4 wk divided by 28 d, averaged 0.172 nmol/ml per d in uremic versus 0.072 nmol/ml per d in control plasma (P < 0.01). The difference in Pentosidine yield between uremic and control plasma was maintained in samples ultrafiltrated through a filter with a 5000-Da cutoff value and fortified with human serum albumin (0.099 versus 0.064 nmol/ml per d; P < 0.05). Pentosidine yield was higher in pre- than in postdialysis plasma samples (0.223 versus 0.153 nmol/ml per d; P < 0.05). These results suggest that a large fraction of the Pentosidine precursors accumulated in uremic plasma have a lower than 5000 Da molecular weight. Addition of aminoguanidine and OPB-9195, which inhibit the Maillard reaction, lowered Pentosidine yield in both uremic and control plasma. When ultrafiltrated plasma was exposed to 2,4-dinitrophenylhydrazine, the yield of hydrazones, formed by interaction with carbonyl groups, was markedly higher in uremic than in control plasma. These observations strongly suggest that the Pentosidine precursors accumulated in uremic plasma are carbonyl compounds. These precursors are unrelated to glucose or ascorbic acid, whose concentration is either normal or lowered in uremic plasma. They are also unrelated to 3-deoxyglucosone, a glucose-derived dicarbonyl compound whose level is raised in uremic plasma: Its addition to normal plasma fails to increase Pentosidine yield. This study reports an elevated level of reactive carbonyl compounds ("carbonyl stress") in uremic plasma. Most have a lower than 5000 Da molecular weight and are thus partly removed by hemodialysis. Their effect on Pentosidine generation can be inhibited by aminoguanidine or OPB-9195. Carbonyl stress might contribute to AGE modification of proteins and thus to clinically relevant complications of uremia.

  • generation of protein carbonyls by glycoxidation and lipoxidation reactions with autoxidation products of ascorbic acid and polyunsaturated fatty acids
    FEBS Letters, 1998
    Co-Authors: Toshio Miyata, Katsunori Horie, Hideto Sakai, Reiko Inagi, Koji Uchida, Koichi Asahi, Yukihiro Yamada, Kiyoshi Kurokawa
    Abstract:

    Accumulation of carbonyl derivatives of proteins (protein carbonyl) is taken as a biomarker of oxidative protein damage in aging and in various diseases. We detected protein carbonyls in situ in human diabetic arteriosclerotic tissues and characterized the formation of protein carbonyls. Protein carbonyls were identified in the thickened intima of arterial walls and co-localized with protein adducts formed by carbonyl amine chemistry between protein and carbonyl compounds derived from autoxidation of carbohydrates, lipids, and ascorbate, i.e. advanced glycation end products or glycoxidation products, such as carboxymethyllysine (CML) and Pentosidine, and lipoxidation products, such as malondialdehyde (MDA) and 4-hydroxy-nonenal (HNE). In vitro incubation of proteins with ascorbic acid accelerated the production of protein carbonyls as well as CML and Pentosidine, and incubation with arachidonate accelerated the production of protein carbonyls as well as CML, MDA, and HNE. By contrast, incubation of proteins with glucose resulted in the production of CML and Pentosidine, but not protein carbonyls. Schiff base inhibitors, (±)-2-isopropylidenehydrazono-4-oxo-thiazolidin-5-ylacetanilide and aminoguanidine, inhibited the production of protein carbonyls after incubation with ascorbate and arachidonate. The present study suggests that ascorbate and polyunsaturated fatty acids, but not glucose, represent potential sources of protein carbonyls, and that both the glycoxidation and lipoxidation reactions contribute to protein carbonyl formation in aging and various diseases.

Ruud A Bank - One of the best experts on this subject based on the ideXlab platform.

  • Pentosidine accumulates in the aging vitreous body a gender effect
    Experimental Eye Research, 2009
    Co-Authors: M Van Deemter, Ruud A Bank, Theodorus L Ponsioen, J M M Snabel, R J Van Der Worp, Johanna M M Hooymans
    Abstract:

    The human vitreous body undergoes structural changes with aging. This can be followed by a posterior vitreous detachment, which can result in ocular pathology. As in many collagenous tissues, age-related changes in the vitreous could be caused by the formation of advanced glycation end products (AGEs). The goal of this study was to find out whether the AGE Pentosidine accumulates in the human vitreous with aging. With this data we were able to estimate the half-life of vitreous collagen. Furthermore, we analyzed whether there was a gender difference in Pentosidine accumulation, as this was seen in other tissues as well. Using high performance liquid chromatography, Pentosidine contents were determined in whole vitreous bodies and in separate parts of vitreous bodies, which were all obtained from human donor eyes. Our results show that Pentosidine accumulates in the human vitreous. From the rate of accumulation we could roughly estimate that vitreous collagen has as a similar or shorter half-life compared to skin collagen. This supports the concept of collagen turnover in the vitreous. In general, the female vitreous experiences a faster Pentosidine accumulation than the male vitreous, and most of the Pentosidine accumulation in the former occurs after 50 years of age.

  • age related accumulation of maillard reaction products in human articular cartilage collagen
    Biochemical Journal, 2000
    Co-Authors: Nicole Verzijl, Esther Oldehinkel, Michael T Bayliss, Johannes W. J. Bijlsma, Jack Degroot, Ruud A Bank, John W. Baynes, Suzanne R. Thorpe, Floris P J G Lafeber, Johan M. Tekoppele
    Abstract:

    Non-enzymic modification of tissue proteins by reducing sugars, the so-called Maillard reaction, is a prominent feature of aging. In articular cartilage, relatively high levels of the advanced glycation end product (AGE) Pentosidine accumulate with age. Higher Pentosidine levels have been associated with a stiffer collagen network in cartilage. However, even in cartilage, Pentosidine levels themselves represent < 1 cross-link per 20 collagen molecules, and as such cannot be expected to contribute sub-stantially to the increase in collagen network stiffness. In the present study, we investigated a broad range of Maillard reaction products in cartilage collagen in order to determine whether Pentosidine serves as an adequate marker for AGE levels. Not only did the well-characterized AGEs Pentosidine, N(e)-(carboxymethyl)lysine, and N(e)-(carboxyethyl)lysine increase with age in cartilage collagen (all P < 0.0001), but also general measures of AGE cross-linking, such as browning and fluorescence (both P < 0.0001), increased. The levels of these AGEs are all higher in cartilage collagen than in skin collagen. As a functional measure of glycation the digestibility of articular collagen by bacterial collagenase was investigated; digestibility decreased linearly with age, proportional to the extent of glycation. Furthermore, the arginine content and the sum of the hydroxylysine and lysine content of cartilage collagen decrease significantly with age (P < 0.0001 and P < 0.01 respectively), possibly due to modification by the Maillard reaction. The observed relationship between glycation and amino acid modification has not been reported previously in vivo. Our present results indicate that extensive accumulation of a variety of Maillard reaction products occurs in cartilage collagen with age. Altogether our results support the hypothesis that glycation contributes to stiffer and more brittle cartilage with advancing age.

  • influence of site and age on biochemical characteristics of the collagen network of equine articular cartilage
    American Journal of Veterinary Research, 1999
    Co-Authors: P A J Brama, Johan M. Tekoppele, Ruud A Bank, P R Van Weeren, A Barneveld
    Abstract:

    Objective - To determine variations in biochemical characteristics of equine articular cartilage in relation to age and the degree of predisposition for osteochondral disease at a specific site. Sample Population - Articular cartilage specimens from 53 horses 4 to 30 years old. Procedure - Healthy specimens were obtained from 2 locations on the proximal articular surface of the first phalanx that had different disease prevalences (site 1 at the mediodorsal margin and site 2 at the center of the medial cavity). Water, total collagen, and hydroxylysine contents and enzymatic (hydroxylysylpyridinoline [HP]) and nonenzymatic (Pentosidine) crosslinking were determined at both sites. Differences between sites were analyzed by ANOVA (factors, site, and age), and age correlation was tested by Pearson's product-moment correlation analysis. Significance was set at P < 0.01. Results - Correlation with age was not found for water, collagen, hydroxylysine contents, and enzymatic cross-linking. Nonenzymatic crosslinking was higher in older horses and was linearly related to age (r = 0.94). Water and collagen contents and HP and Pentosidine crosslinks were significantly higher at site 1. Hydroxylysine content was significantly lower at site 1. Conclusions - Except for nonenzymatic glycation, the composition of articular cartilage collagen does not change significantly in adult horses. A significant topographic variation exists in biochemical characteristics of the articular cartilage collagen network in equine metacarpophalangeal joints. These differences may influence local biomechanical properties and, hence, susceptibility to osteochondral disease, as will greater Pentosidine crosslinks in older horses that are likely to cause stiffer and more brittle cartilage.

  • Age-related decrease in proteoglycan synthesis of human articular chondrocytes: the role of nonenzymatic glycation.
    Arthritis and rheumatism, 1999
    Co-Authors: Jeroen Degroot, Johannes W. J. Bijlsma, Nicole Verzijl, Ruud A Bank, Floris P J G Lafeber, Johan M. Tekoppele
    Abstract:

    Objective. To examine the effect of nonenzymatic glycation of cartilage extracellular matrix on the synthetic activity of chondrocytes. Methods. The proteoglycan-synthesis rate (35SO42- incorporation) and levels of advanced nonenzymatic glycation (determined by high-performance liquid chromatography measurement of Pentosidine) were evaluated in human articular cartilage from 129 donors, varying in age from 25 to 88 years, and in cartilage with enhanced levels of advanced glycation end-products (AGEs) resulting from incubation with ribose. Results. Cartilage showed a strong age-related increase in Pentosidine levels (r = 0.97, P < 0.0005) and, concomitantly, a decrease in proteoglycan synthesis (r = -0.98, P < 0.0002). This decrease in proteoglycan synthesis correlated with the increase in Pentosidine (r = -0.95, P < 0.02). Moreover, the elevation of Pentosidine levels in the in vitro-ribosylated cartilage was proportional with the decrease in proteoglycan synthesis (r = -0.95, P < 0.005). Conclusion. In both aged and in vitro AGE-enriched cartilage, the rate of proteoglycan synthesis was negatively correlated with the degree of glycation. This suggests that the age-related increase in cartilage AGE levels may be responsible, at least in part, for the age-related decline in the synthetic capacity of cartilage.

  • ageing and zonal variation in post translational modification of collagen in normal human articular cartilage the age related increase in non enzymatic glycation affects biomechanical properties of cartilage
    Biochemical Journal, 1998
    Co-Authors: Ruud A Bank, Michael T Bayliss, Floris P J G Lafeber, A Maroudas, Johan M. Tekoppele
    Abstract:

    A biomechanical failure of the collagen network is postulated in many hypotheses of the development of osteoarthritis with advancing age. Here we investigate the accumulation of non-enzymatic glycation (NEG) products in healthy human articular cartilage, its relation to tissue remodelling and its role in tissue stiffening. Pentosidine levels were low up to age 20 years, and increased linearly after this age. This indicates extensive tissue remodelling at young age, and slow turnover of collagen after maturity has been reached. The slow remodelling is supported by the finding that enzymatic modifications of collagen (hydroxylysine, hydroxylysylpyridinoline, and lysylpyridinoline) were not related to age. The high remodelling is supported by levels of the crosslink lysylpyridinoline (LP) as a function of distance from the articular surface. LP was highest at the surface in mature cartilage (> 20 years), whereas in young cartilage (< 10 years) the opposite was seen; highest levels were close to the bone. LP levels in cartilage sections at age 14 years are high at the surface and close to the bone, but they are low in the middle region. This indicates that maturation of cartilage in the second decade of life starts in the upper half of the tissue, and occurs last in the tissue close to the bone. The effect of NEG products on instantaneous deformation of cartilage was investigated as a functional of topographical variations in Pentosidine levels in vivo and in relation to in vitro induced NEG. Consistently, higher Pentosidine levels were associated with a stiffer collagen network. A stiffer and more crosslinked collagen network may become more brittle and more prone to fatigue.

Vincent M. Monnier - One of the best experts on this subject based on the ideXlab platform.

  • the impact of salsalate treatment on serum levels of advanced glycation end products in type 2 diabetes
    Diabetes Care, 2014
    Co-Authors: Joshua I Barzilay, Steven E Shoelson, Allison B Goldfine, Vivian Fonseca, Kathleen A Jablonski, Christopher Strauch, Vincent M. Monnier
    Abstract:

    measured in patient serum samples. RESULTS Forty-eight weeks of salsalate treatment lowered levels of HbA1c and serum furosine (P < 0.001) and CML compared with placebo. The AGEs CEL and G- 1 Ha nd MG- 1 H levels were unchanged, whereas Pentosidine levels increased more than twofold (P < 0.001). Among salsalate users, increases in adiponectin levels were associated with lower HbA1c levels during follow-up (P < 0.001). Changes in renal and inflammation factor levels were not associated with changes in levels of early or late glycation factors. Pentosidine level changes were unrelated to changes in levels of renal function, inflammation, or cytokines. CONCLUSIONS

  • advanced glycation end products as markers of aging and longevity in the long lived ansell s mole rat fukomys anselli
    Journals of Gerontology Series A-biological Sciences and Medical Sciences, 2012
    Co-Authors: Philip Dammann, David R Sell, Christopher Strauch, Sabine Begall, Vincent M. Monnier
    Abstract:

    Mole-rat of the genus Fukomys are mammals whose life span is strongly influenced by reproductive status with breeders far outliving nonbreeders. This raises the important question of whether increased longevity of the breeders is reflected in atypical expression of biochemical markers of aging. Here, we measured markers of glycation and advanced glycation end-products formed in insoluble skin collagen of Ansell’s mole-rat Fukomys anselli as a function of age and breeding status. Glucosepane, Pentosidine, and total advanced glycation end-product content significantly increased with age after correction for breeder status and sex. Unexpectedly, total advanced glycation end-products, glucosepane, and carboxymethyl-lysine (CML) were significantly higher in breeders versus nonbreeders suggesting that breeders have evolved powerful defenses against combined oxidant and carbonyl stress compared with nonbreeders. Most interestingly, when compared with other mammals, Pentosidine formation rate was lower in mole-rat compared with other short-lived rodents confirming previous observations of an inverse relationship between longevity and Pentosidine formation rates in skin collagen.

  • skin collagen glycation glycoxidation and crosslinking are lower in subjects with long term intensive versus conventional therapy of type 1 diabetes relevance of glycated collagen products versus hba1c as markers of diabetic complications dcct skin c
    Diabetes, 1999
    Co-Authors: Vincent M. Monnier, David R Sell, Patricia A Cleary, John M Lachin, Oliver M Bautista, David Kenny, John Fogarty, William Dahms, Saul Genuth
    Abstract:

    The relationships between long-term intensive control of glycemia and indicators of skin collagen glycation (furosine), glycoxidation (Pentosidine and N(epsilon)-[carboxymethyl]-lysine [CML]), and crosslinking (acid and pepsin solubility) were examined in 216 patients with type 1 diabetes from the primary prevention and secondary intervention cohorts of the Diabetes Control and Complications Trial. By comparison with conventional treatment, 5 years of intensive treatment was associated with 30-32% lower furosine, 9% lower Pentosidine, 9-13% lower CML, 24% higher acid-soluble collagen, and 50% higher pepsin-soluble collagen. All of these differences were statistically significant in the subjects of the primary prevention cohort (P

  • immunohistochemical colocalization of glycoxidation products and lipid peroxidation products in diabetic renal glomerular lesions implication for glycoxidative stress in the pathogenesis of diabetic nephropathy
    Journal of Clinical Investigation, 1997
    Co-Authors: Katsunori Horie, Vincent M. Monnier, Toshio Miyata, Kayo Maeda, S Miyata, Satoshi Sugiyama, Hideto Sakai, C Van Ypersole De Strihou, Joseph L Witztum, Kiyoshi Kurokawa
    Abstract:

    Advanced glycation end products (AGEs) include a variety of protein adducts whose accumulation alters the structure and function of tissue proteins and stimulates cellular responses, They have been implicated in tissue damage associated with diabetic complications, To assess the possible link between AGE accumulation and the development of diabetic nephropathy (DN), we have examined the immunohistochemical localization of various AGE structures postulated to date, i.e., Pentosidine, N-epsilon-(carboxymethyl)lysine (CML), and pyrraline, in diabetic and control kidneys. CML and Pentosidine accumulate in the expanded mesangial matrix and thickened glomerular capillary walls of early DN and in nodular lesions and arterial walls of advanced DN, but were absent in control kidneys, By contrast, pyrraline was not found within diabetic glomeruli but was detected in the interstitial connective tissue of both normal and diabetic kidneys, Although the distribution of pyrraline was topographically identical to type III collagen, distribution of Pentosidine and CML was not specific for collagen type, suggesting that difference in matrix protein composition per se could not explain heterogeneous AGE localization. Since oxidation is linked closely to the formation of Pentosidine and CML, we also immunostained malondialdehyde (MDA), a lipid peroxidation product whose formation is accelerated by oxidative stress, assuming that local oxidative stress may serve as a mechanism of Pentosidine and CML accumulation, Consistent with our assumption, diabetic nodular lesions were stained positive for MDA. These findings show that AGE localization in DN varies according to AGE structure, and suggest that the colocalization of markers of glycoxidation (Pentosidine and CML) with a marker of lipid peroxidation reflects a local oxidative stress in association with the pathogenesis of diabetic glomerular lesions, Thus, glycoxidation markers may serve as useful biomarkers of oxidative damage in DN.

  • age related association of tail tendon break time with tissue Pentosidine in dba 2 vs c57bl 6 mice the effect of dietary restriction
    Journals of Gerontology Series A-biological Sciences and Medical Sciences, 1997
    Co-Authors: David R Sell, Vincent M. Monnier
    Abstract:

    In recent years, there has been a growing interest in the development of a panel of biomarkers useful in the evaluation of interventions on aging processes. An ideal marker should change with age, be related to species longevity, and respond to the effects of dietary restriction, which is the only intervention currently known to increase species longevity. In the present study, we compared parameters of collagen aging (i.e., tail tendon break time [TBT] and the glycoxidation product Pentosidine) in tendon, ear, and skin of two species of rodents with different life spans: the shorter-lived DBA/2 versus the longer-lived C57BLJ6 mouse strains. Both TBT and tissue Pentosidine significantly increased with age in both strains of mice. The rate of increase for TBT and Pentosidine occurred faster for the DBA/2 compared with the C57BLJ6 strain. Dietary restriction significantly inhibited the age-related increase of TBT and Pentosidine formation rate in DBA/2 mice. In C57BU6 mice, the age-related increase of TBT was significantly inhibited by dietary restriction. However, except for tendon at 24 months, Pentosidine level was not affected by dietary restriction. These studies show that the rate of collagen aging, as reflected by TBT and glycoxidation, increases proportionally with age, and that these rate increases are related to longevity in two strains of mice. Pentosidine can be monitored with age just as well in a piece of easily accessible ear tissue as in skin or tendon. Thus, Pentosidine is expected to be a useful and easily measurable noninvasive marker in future intervention studies on aging.

Kiyoshi Kurokawa - One of the best experts on this subject based on the ideXlab platform.

  • accumulation of carbonyls accelerates the formation of Pentosidine an advanced glycation end product carbonyl stress in uremia
    Journal of The American Society of Nephrology, 1998
    Co-Authors: Toshio Miyata, Kiyoshi Kurokawa, Yasuhiko Ueda, Y Yamada, Y Izuhara, Takehiko Wada, Michel Jadoul, Akira Saito, C Van Ypersele De Strihou
    Abstract:

    Advanced glycation end product (AGE) formation is related to hyperglycemia in diabetes but not in uremia, because plasma AGE levels do not differ between diabetic and nondiabetic hemodialysis patients. The mechanism of this phenomenon remains elusive. Previously, it was suggested that elevation of AGE levels in uremia might result from the accumulation of unknown AGE precursors. The present study evaluates the in vitro generation of Pentosidine, a well identified AGE structure. Plasma samples from healthy subjects and nondiabetic hemodialysis patients were incubated under air for several weeks. Pentosidine levels were determined al:intervals by HPLC assay. Pentosidine rose to a much larger extent in uremic than in control plasma. Pentosidine yield, i.e., the change in Pentosidine level between 0 and 4 wk divided by 28 d, averaged 0.172 nmol/ml per d in uremic versus 0.072 nmol/ml per d in control plasma (P < 0.01). The difference in Pentosidine yield between uremic and control plasma was maintained in samples ultrafiltrated through a filter with a 5000-Da cutoff value and fortified with human serum albumin (0.099 versus 0.064 nmol/ml per d; P < 0.05). Pentosidine yield was higher in pre- than in postdialysis plasma samples (0.223 versus 0.153 nmol/ml per d; P < 0.05). These results suggest that a large fraction of the Pentosidine precursors accumulated in uremic plasma have a lower than 5000 Da molecular weight. Addition of aminoguanidine and OPB-9195, which inhibit the Maillard reaction, lowered Pentosidine yield in both uremic and control plasma. When ultrafiltrated plasma was exposed to 2,4-dinitrophenylhydrazine, the yield of hydrazones, formed by interaction with carbonyl groups, was markedly higher in uremic than in control plasma. These observations strongly suggest that the Pentosidine precursors accumulated in uremic plasma are carbonyl compounds. These precursors are unrelated to glucose or ascorbic acid, whose concentration is either normal or lowered in uremic plasma. They are also unrelated to 3-deoxyglucosone, a glucose-derived dicarbonyl compound whose level is raised in uremic plasma: Its addition to normal plasma fails to increase Pentosidine yield. This study reports an elevated level of reactive carbonyl compounds ("carbonyl stress") in uremic plasma. Most have a lower than 5000 Da molecular weight and are thus partly removed by hemodialysis. Their effect on Pentosidine generation can be inhibited by aminoguanidine or OPB-9195. Carbonyl stress might contribute to AGE modification of proteins and thus to clinically relevant complications of uremia.

  • generation of protein carbonyls by glycoxidation and lipoxidation reactions with autoxidation products of ascorbic acid and polyunsaturated fatty acids
    FEBS Letters, 1998
    Co-Authors: Toshio Miyata, Katsunori Horie, Hideto Sakai, Reiko Inagi, Koji Uchida, Koichi Asahi, Yukihiro Yamada, Kiyoshi Kurokawa
    Abstract:

    Accumulation of carbonyl derivatives of proteins (protein carbonyl) is taken as a biomarker of oxidative protein damage in aging and in various diseases. We detected protein carbonyls in situ in human diabetic arteriosclerotic tissues and characterized the formation of protein carbonyls. Protein carbonyls were identified in the thickened intima of arterial walls and co-localized with protein adducts formed by carbonyl amine chemistry between protein and carbonyl compounds derived from autoxidation of carbohydrates, lipids, and ascorbate, i.e. advanced glycation end products or glycoxidation products, such as carboxymethyllysine (CML) and Pentosidine, and lipoxidation products, such as malondialdehyde (MDA) and 4-hydroxy-nonenal (HNE). In vitro incubation of proteins with ascorbic acid accelerated the production of protein carbonyls as well as CML and Pentosidine, and incubation with arachidonate accelerated the production of protein carbonyls as well as CML, MDA, and HNE. By contrast, incubation of proteins with glucose resulted in the production of CML and Pentosidine, but not protein carbonyls. Schiff base inhibitors, (±)-2-isopropylidenehydrazono-4-oxo-thiazolidin-5-ylacetanilide and aminoguanidine, inhibited the production of protein carbonyls after incubation with ascorbate and arachidonate. The present study suggests that ascorbate and polyunsaturated fatty acids, but not glucose, represent potential sources of protein carbonyls, and that both the glycoxidation and lipoxidation reactions contribute to protein carbonyl formation in aging and various diseases.

  • immunohistochemical colocalization of glycoxidation products and lipid peroxidation products in diabetic renal glomerular lesions implication for glycoxidative stress in the pathogenesis of diabetic nephropathy
    Journal of Clinical Investigation, 1997
    Co-Authors: Katsunori Horie, Vincent M. Monnier, Toshio Miyata, Kayo Maeda, S Miyata, Satoshi Sugiyama, Hideto Sakai, C Van Ypersole De Strihou, Joseph L Witztum, Kiyoshi Kurokawa
    Abstract:

    Advanced glycation end products (AGEs) include a variety of protein adducts whose accumulation alters the structure and function of tissue proteins and stimulates cellular responses, They have been implicated in tissue damage associated with diabetic complications, To assess the possible link between AGE accumulation and the development of diabetic nephropathy (DN), we have examined the immunohistochemical localization of various AGE structures postulated to date, i.e., Pentosidine, N-epsilon-(carboxymethyl)lysine (CML), and pyrraline, in diabetic and control kidneys. CML and Pentosidine accumulate in the expanded mesangial matrix and thickened glomerular capillary walls of early DN and in nodular lesions and arterial walls of advanced DN, but were absent in control kidneys, By contrast, pyrraline was not found within diabetic glomeruli but was detected in the interstitial connective tissue of both normal and diabetic kidneys, Although the distribution of pyrraline was topographically identical to type III collagen, distribution of Pentosidine and CML was not specific for collagen type, suggesting that difference in matrix protein composition per se could not explain heterogeneous AGE localization. Since oxidation is linked closely to the formation of Pentosidine and CML, we also immunostained malondialdehyde (MDA), a lipid peroxidation product whose formation is accelerated by oxidative stress, assuming that local oxidative stress may serve as a mechanism of Pentosidine and CML accumulation, Consistent with our assumption, diabetic nodular lesions were stained positive for MDA. These findings show that AGE localization in DN varies according to AGE structure, and suggest that the colocalization of markers of glycoxidation (Pentosidine and CML) with a marker of lipid peroxidation reflects a local oxidative stress in association with the pathogenesis of diabetic glomerular lesions, Thus, glycoxidation markers may serve as useful biomarkers of oxidative damage in DN.

  • immunohistochemical localization of advanced glycation end products Pentosidine and carboxymethyllysine in lipofuscin pigments of alzheimer s disease and aged neurons
    Biochemical and Biophysical Research Communications, 1997
    Co-Authors: Katsunori Horie, Toshio Miyata, Takeshi Yasuda, Akinori Takeda, Yoshinari Yasuda, Kenji Maeda, Gen Sobue, Kiyoshi Kurokawa
    Abstract:

    Lipofuscins are intracellular fluorescent pigments accumulating in the central nervous system (CNS) with aging and degenerative processes such as Alzheimer's disease (AD). Although they are thought to be lipid peroxidation products derived from malondialdehyde, their biogenesis remains controversial. We further characterize the chemical nature of lipofuscins in brain tissues from AD patients and normal aged subjects. Advanced glycation end products (AGEs), Pentosidine and carboxymethyllysine (CML), were identified by appropriate specific antibodies. They have physicochemical properties similar to those of lipofuscin and also increase with aging. Pentosidine and CML were identified in the neuronal perikarya and the extraneuroperikaryal deposits of both the AD and aged brain. Pentosidine, but not CML, was present in the fiber-like structure within the neuropil and the core of classical senile plaque. In the brain of young subjects without CNS disease, Pentosidine and CML staining was faint. Pentosidine and CML co-localized with lipofuscin pigments in the neuronal perikarya of both the AD and aged brain. We demonstrate for the first time that lipofuscin is constituted not only of lipid peroxidation products but also from glycation products which may be the origin of fluorescent pigments. Lipofuscins should thus be considered as fluorescent pigments generated by lipid- and sugar-derived Schiff base-protein polymers.

  • implication of an increased oxidative stress in the formation of advanced glycation end products in patients with end stage renal failure
    Kidney International, 1997
    Co-Authors: Toshio Miyata, Katsunori Horie, Yoshinari Yasuda, Kenji Maeda, Kiyoshi Kurokawa, Yoshiyasu Iida, Yoshinao Wada, Zhe Cai, C Van Ypersele De Strihou
    Abstract:

    Implication of an increased oxidative stress in the formation of advanced glycation end products in patients with end-stage renal failure. Recent studies have demonstrated a marked increase in the level of advanced glycation end products (AGEs) in the plasma, skin and amyloid fibrils of hemodialysis (HD) patients. The presence of AGEs in ( β 2 m) forming amyloid fibrils has been established in a previous immunochemical study relying on a monoclonal anti-AGE antibody. In the present study, Western blot analysis and immunohistochemistry reveal that the epitope recognized by this antibody is N e -(carboxymethyl)lysine (CML) and that CML is one of the AGE structures present in amyloid fibrils. Thus, two AGE structures, CML and Pentosidine, are now recognized in dialysis-related amyloidosis. AGE accumulation in uremia is not accounted for by elevated glucose levels. Since CML and Pentosidine formation are closely linked to oxidative processes, we tested the hypothesis that a high oxidative stress enhanced AGE formation in HD patients. We focused on ascorbic acid (AA) because AA is easily oxidized under oxidative stress and its oxidized form (oxiAA) is a source of CML and Pentosidine. In vitro incubation of β 2 m with AA under atmospheric oxygen resulted in: (1) the rapid appearance of characteristic physicochemical properties of AGEs (brown color, fluorescence, polymerization tendency); (2) the transformation of β 2 m into AGE-modified β 2 m recognized by a specific monoclonal antibody; and (3) the accelerated formation of CML in β 2 m and β 2 m-peptide, recognized by mass spectrometry. A similar in vitro incubation of human serum albumin disclosed a parallel production of Pentosidine measured by high-performance liquid chromatographic assay. In HD patients, the degree of AA oxidation, assessed as the ratio of oxiAA to total ascorbate, was more than twice as high as that of normal subjects (0.87 ± 0.16 vs. 0.35 ± 0.11, P P r 2 = 0.25) and free ( P r 2 = 0.22) Pentosidine. Altogether these results demonstrate that AGE, that is, CML and Pentosidine, production is accelerated under oxidative stress, even in the absence of glucose. They suggest that, in uremia, CML and Pentosidine production is determined both by an increased oxidative stress and the availability of precursors such as oxiAA. Finally, both CML and Pentosidine contribute to the AGEs present in dialysis-related amyloid fibrils.