Evidence for glucose-mediated covalent cross-linking of collagen after glycosylation <i>in vitro</i>

Kent, M J C; Light, Nicholas; Bailey, Allen J.

doi:10.1042/bj2250745

Cited by 165 publications

(74 citation statements)

References 25 publications

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“…Second, densitometric analysis of electrophoretic profiles of TBM extracts detected more high molecular weight material in glucosetreated samples compared to control. These findings are typical for tissues that have become crosslinked as a result ofglycation (17,18,(20)(21)(22). Finally, fluorometric analysis detected increased fluorescence in glucose-treated TBM compared to ribitol-treated TBM at two different wavelengths that detect glycation-generated crosslinks (Fig.…”

Section: Resultsmentioning

confidence: 76%

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Nonenzymatic glycosylation-induced modifications of intact bovine kidney tubular basement membrane.

Anderson¹,

Tsilibary²,

Charonis³

1993

J. Clin. Invest.

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We examined structural changes in bovine kidney tubular basement membrane (TBM) following in vitro nonenzymatic glycosylation (NEG). Isolated TBM was incubated for 2 wk at 370C in the absence of sugar or in the presence of either glucose or ribitol under conditions that minimized degradation and oxidative damage. NEG and crosslink formation in glycated TBM were confirmed by decreased solubility, increased amounts of low mobility material by SDS-PAGE, and increased specific fluorescence compared to controls. Morphological analysis using high resolution, low voltage scanning electron microscopy (LV-SEM) revealed a complex three-dimensional meshwork of interconnecting strands with intervening openings. Glycated TBM underwent distinct morphological changes, including a 58% increase in the amount of image surface area occupied by openings. This was due to an apparent increase in the number of large openings (diameters > 12.5 nm), whereas the number of small openings (diameters < 12.5 nm) remained unchanged. These findings corroborate earlier physiological studies, which established that the loss of glomerular permselectivity seen in patients with diabetic nephropathy is due to the formation of large pores in the kidney filtration barrier of which the BM is a major component. We conclude that NEG and crosslink formation among BM components lead to modifications of BM ultrastructure, which could play a role in loss of barrier function in diabetic microangiopathy and nephropathy. (J. Clin. Invest. 1993. 92:3045-3052.)

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Section: Resultsmentioning

confidence: 76%

“…It is well established that incubation with reducing sugars leads to the generation of glycated and crosslinked proteins in vitro (6,(16)(17)(18)(19). In order to document such changes in our experiments, TBM, which had been incubated as described in Methods, was solubilized and examined by electrophoresis and fluorometric analysis.…”

Section: Resultsmentioning

confidence: 99%

Nonenzymatic glycosylation-induced modifications of intact bovine kidney tubular basement membrane.

Anderson¹,

Tsilibary²,

Charonis³

1993

J. Clin. Invest.

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“…The advanced stage of glycation involves a variety of reactions, such as oxidation, fragmentation, and crosslinking, giving rise to heterogeneous products called advanced glycation end products (AGEs) (Dunn et al, 1989;Hayase et al, 1989;Grandhee and Monnier, 1991;Fu et al, 1994). A cross-linking reaction leads to the formation of insoluble aggregates of proteins (Kent et al, 1985;Reiger, 1991). Several proteins, such as hemoglobin (Bunn et al, 1978;Shapiro et al, 1980), albumin (Day et al, 1979;Iberg and Fluckiger, 1986), collagen (Robins and Bailey, 1972;Reiger et al, 1992), and lens crystallins (Stevens et al, 1978;Pande et al, 1979), and also some enzymes (Agarwal et al, 1985;Arai et al, 1987;McPherson et al, 1988) are known to undergo glycation in vivo.…”

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confidence: 99%

Characterization of In Vitro Glycation Sites of Tau

Nacharaju

Yen

1997

Journal of Neurochemistry

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Tau is a microtubule-associated protein that loses microtubule binding activity and aggregates into paired helical filaments (PHFs) in Alzheimer's disease. Nonenzymic glycation is one of the posttranslational modifications detected in PHF-tau, but not in normal tau. PHF-tau has reduced ability to bind to microtubules. To determine whether glycation of tau occurs in its microtubule binding domains, we have characterized in vitro glycation sites of the longest isoform of tau, which has four microtubule binding domains (Tau-4). The identified glycation sites are 132, 150, 163, 174, 225, 234, 259, 280, 281, 347, 353, and 369. We have also studied glycation of another isoform of tau, which has only three microtubule binding domains (Tau-3). This isoform is modified by glucose 15-20% more slowly than Tau-4. However, the glycation sites appear to be the same in both isoforms, except for Lys-280 and 281; these are located in the second microtubule binding domain, which is missing in Tau-3. Lys-150, 163, and 174 are located within or proximal to the sequence of tau that is involved in the microtubule nucleation activity, and 280, 281, 347, 353, and 369 are located in the microtubule binding domains. Glycation at these sites can affect the functional properties of tau, and advanced glycation at these sites might lead to the formation of insoluble aggregates similar to the ones seen in Alzheimer's disease.

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“…Self-aggregation to the collagen IV-network may be a function of the terminal domains, whereas binding of ligands, e. g. laminin and heparansulphate-proteoglycan [54±56] and interaction with adjacent cells [57,17] can be attributed to the central triple-helical domain which is also a target for glycoxidative reactions. The impairment of one or some of these functions of collagen IV might be responsible for the decrease in renal performance in incipient diabetes mellitus [58].…”

Section: Discussionmentioning

confidence: 99%

Biochemical and biophysical alterations of the 7S and NC1 domain of collagen IV from human diabetic kidneys

et al. 1998

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Glycation and glycoxidative reactions have been recognised to be a major pathogenetic principle for biochemical and biophysical alterations of proteins in diabetes mellitus [1±3]. Both processes have been shown to increase in humans with age and even more in patients with diabetes mellitus with the duration of the disease [4±8].Glycoxidative reactions, e. g. the Maillard reaction, are initiated by the condensation of a reducing sugar with an e-amino group of lysyl-or hydroxylysyl-residues of proteins [9]. The resulting Schiff-base is stabilised subsequently by Amadori rearrangement and processed further in very diverse and not yet fully elucidated chemical reactions resulting in a variety of cross-linked compounds. Only a small number of those, including pentosidine, have been characterised in structure and chemical composition [2, 10±16]. Glycation of proteins is associated with the formation of high-molecular aggregates that are stabilised by non-reducible cross-linking components [13, 17±18] with characteristic fluorescence spectra [6,19,20]. Circular dichroism (CD) spectroscopy studies of glycated proteins exhibited a damaging effect of the modifications on protein structure and stability [21,22].In diabetic nephropathy the disordered morphology and functional deficiency of the glomerular basement membrane (GBM) has been explained by glycation of the collagen IV network providing the mechanical scaffold of the membrane texture. Collagen IV monomers consist of a collagenous major triplehelical domain with two specific cross-linking domains, the NC1 domain at the C-terminal end and the N-terminus the 7S domain [23±26], facilitating Diabetologia (1998) Summary Glycation of basement membrane collagen IV has been implicated as a major pathogenetic process leading to diabetic microvascular complications. To evaluate the relevance of carbohydrate-induced modifications on collagen IV in diabetic nephropathy, we isolated the cross-linking domains 7S and NC1 from the glomerular basement membrane (GBM) of patients with diabetes mellitus. Modifications characteristic for glycated proteins were identified when the domains from diabetic kidney were compared with the same domains from human placenta as an unmodified control. In both domains a marked formation of inter-and intramolecular cross links could be demonstrated by SDS-PAGE. Furthermore circular dichroism studies showed a decrease in helicity of the 7S domain from human diabetic kidneys of 13 %, indicating denaturation already at room temperature. Thermal transition profiles, showing a shift of the denaturation temperature towards a lower temperature, with loss of a distinct second melting point, confirmed this observation. Our data provide further evidence for a possible role of protein-modification by glycoxidative reactions in the onset of diabetic nephropathy in vivo. [Diabetologia (1998

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Evidence for glucose-mediated covalent cross-linking of collagen after glycosylation in vitro

Cited by 165 publications

References 25 publications

Nonenzymatic glycosylation-induced modifications of intact bovine kidney tubular basement membrane.

Nonenzymatic glycosylation-induced modifications of intact bovine kidney tubular basement membrane.

Characterization of In Vitro Glycation Sites of Tau

Biochemical and biophysical alterations of the 7S and NC1 domain of collagen IV from human diabetic kidneys

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