The role of glycation cross-links in diabetic vascular stiffening

Sims, Trevor J.; Rasmussen, L. M.; Oxlund, Hans; Bailey, Allen J.

doi:10.1007/bf00403914

Cited by 233 publications

(118 citation statements)

References 26 publications

Supporting

Mentioning

111

Contrasting

Unclassified

Order By: Relevance

“…A similar effect was observed on digestion with trypsin followed by chymotrypsin of ribonuclease glycated with phenylglyoxal [25]. This demonstrates a general property of AGE resistance to proteolytic degradation and the tendency to form insoluble aggregates in cells and tissues [5,7].…”

Section: Discussionsupporting

confidence: 71%

See 1 more Smart Citation

Inhibition of human muscle-specific enolase by methylglyoxal and irreversible formation of advanced glycation end products

Gamian

Staniszewska

Danielewicz

2009

Journal of Enzyme Inhibition and Medicinal Chemistry

View full text Add to dashboard Cite

Methylglyoxal (MG) was studied as an inhibitor and effective glycating factor of human muscle-specific enolase. The inhibition was carried out by the use of a preincubation procedure in the absence of substrate. Experiments were performed in anionic and cationic buffers and showed that inhibition of enolase by methylglyoxal and formation of enolasederived glycation products arose more effectively in slight alkaline conditions and in the presence of inorganic phosphate. Incubation of 15 micromolar solutions of the enzyme with 2 mM, 3.1 mM and 4.34 mM MG in 100 mM phosphate buffer pH 7.4 for 3 h caused the loss a 32%, 55% and 82% of initial specific activity, respectively. The effect of MG on catalytic properties of enolase was investigated. The enzyme changed the K M value for glycolytic substrate 2-phospho-D-glycerate (2-PGA) from 0.2 mM for native enzyme to 0.66 mM in the presence of MG. The affinity of enolase for gluconeogenic substrate phosphoenolpyruvate altered after preincubation with MG in the same manner, but less intensively. MG has no effect on V max and optimal pH values. Incubation of enolase with MG for 0-48 h generated high molecular weight protein derivatives. Advanced glycation end products (AGEs) were resistant to proteolytic degradation by trypsin. Magnesium ions enhanced the enzyme inactivation by MG and facilitated AGEs formation. However, the protection for this inhibition in the presence of 2-PGA as glycolytic substrate was observed and AGEs were less effectively formed under these conditions.

show abstract

Section: Discussionsupporting

confidence: 71%

“…Moreover, as a result, a heterogeneous mixture is formed of highly crosslinked protein derivatives, advanced glycation endproducts (AGEs) [4 -6]. Glycated proteins are less soluble and become resistant to proteolysis [6,7]. They are immunogenic and cytotoxic [8,9].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of human muscle-specific enolase by methylglyoxal and irreversible formation of advanced glycation end products

Gamian

Staniszewska

Danielewicz

2009

Journal of Enzyme Inhibition and Medicinal Chemistry

View full text Add to dashboard Cite

show abstract

“…Glycoxidative damage to the artery wall is known to alter vascular function through increasing permeability, 32 vascular stiffening, 56 and LDL binding, 7 all parameters that play a role in the progression of atherosclerosis. Therefore, our studies support a new antiatherogenic role for estradiol at the site of the artery wall.…”

Section: Discussionmentioning

confidence: 99%

17β-Estradiol Reduces Glycoxidative Damage in the Artery Wall

Walsh

Busch

Mullick

et al. 1999

ATVB

View full text Add to dashboard Cite

Abstract-Glycoxidative damage in the vasculature has been linked to atherosclerotic cardiovascular disease. Estrogens protect against the development and progression of atherosclerosis. Because estrogens are potent antioxidants that also effect glucose metabolism, part of their protection against atherosclerosis could be through attenuation of glycoxidative damage in the vascular wall. In this study, we tested the hypothesis that chronic estradiol administration is associated with decreased levels of glycoxidative damage in arterial walls. We harvested and examined iliac arteries from ovariectomized, 8-month-old rats that had been implanted for 6 months with 1 of the following subcutaneous hormone pellets: low estradiol (2.5 mg estradiol), high estradiol (25 mg estradiol), P 4 (200 mg progesterone), low estradiol and P 4 , placebo (no hormone), or control (no implant). Using pentosidine as a biomarker of glycoxidative damage, we found that all vessels from rats receiving estradiol (low estradiol, high estradiol, and low estradiolϩP 4 ) exhibited a 50% reduction in glycoxidative damage compared with P 4 , placebo, and control vessels (PϽ0.05). Consistent with this finding, we observed that estradiol-treated rats had a 30% decrease in tissue levels of hydroperoxides, a marker of oxidative stress. Finally, estradiol-treated rats had a small, but significant, decrease in plasma glucose levels (PϽ0.01). In summary, we report the novel finding that chronic estrogen administration is associated with significant decreases in glycoxidative damage and oxidative stress in the arterial wall. It seems likely that these actions may constitute a mechanism by which estrogen attenuates the progression of atherosclerosis.

show abstract

“…The age-related accumulation of high levels of AGEs in articular cartilage collagen may contribute to the observed stiffening of the cartilage collagen network with advancing age [7,51]. The increased stiffness might make the cartilage collagen network more brittle, as described for vascular tissues [52], and as such impair the resistance of articular collagen to fatigue and predispose aged cartilage to damage and eventual degeneration. Thus the accumulation of AGEs represents a conceivable molecular mechanism whereby age is a predisposing factor for the development of osteoarthritis [7].…”

Section: Maillard Reaction Products In Cartilage Compared With Skin Amentioning

confidence: 99%

Age-related accumulation of Maillard reaction products in human articular cartilage collagen

Verzijl

DeGroot

Oldehinkel³

et al. 2000

Biochemical Journal

242

100

View full text Add to dashboard Cite

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 substantially 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 ε -(carboxymethyl)lysine, and N ε -(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. INTRODUCTIONDuring aging, long-lived proteins such as collagen and eye lens proteins are non-enzymically modified by reducing sugars. The major initial product is fructose-lysine (FL) [1,2], which results from glycation of ε-amino groups on lysine residues. In subsequent Maillard or browning reactions, products known as advanced glycation end products (AGEs) are formed from FL [3,4], and accumulate with age in long-lived proteins [1,2,[5][6][7][8]. These AGEs include structurally characterized adducts, such as N ε -(carboxymethyl)lysine (CML) [1][2][3] and N ε -(carboxyethyl)-lysine (CEL) [9], fluorescent cross-links, such as pentosidine formed between lysine and arginine residues [5,10], as well as chemically unidentified compounds which result in proteinbound browning or fluorescence, and cross-linking [11][12][13][14].In comparison with other collagen-rich tissues such as skin, cartilage contains relatively large amounts of pentosidine [5,15]. Pentosidine levels in articular cartilage increase linearly with age [6-8], as was previously described for skin collagen [16] and lens proteins [10]. Pentosidine is also present in the proteoglycans in articular cartilage [17], but appears to be localized predominantly in the collagen component of the tissue [7]. Age-related accumulation of AGE cross-links in articular cartilage collagen may result in increased stiffening of the collagen network, as was shown after in itro ribosylation of cartilage [7]. Thus AGE cross-linking in i o may contribute to the age-related impairment of the ability of articular collagen to resist mechanically induced damage and eventually cartilage degeneration [18][19][20].Abbreviations used : AGE, advanced glycation end product ; CEL, N ε -(carboxyethyl)lysine ; CML, N ε -(carboxymethyl)lysine ; FL, fructose-lysine. 1 To whom correspondence should be addressed (e-mail JM.TeKoppele!pg.tno.nl).As a functional measure of glycation the digestibility o...

show abstract

The role of glycation cross-links in diabetic vascular stiffening

Cited by 233 publications

References 26 publications

Inhibition of human muscle-specific enolase by methylglyoxal and irreversible formation of advanced glycation end products

Inhibition of human muscle-specific enolase by methylglyoxal and irreversible formation of advanced glycation end products

17β-Estradiol Reduces Glycoxidative Damage in the Artery Wall

Age-related accumulation of Maillard reaction products in human articular cartilage collagen

Contact Info

Product

Resources

About