Laminin Alterations After In Vitro Nonenzymatic Glycosylation

Charonis, Aristidis S.; Reger, Lorrel A.; Dege, J. E.; Kouzi-Koliakos, Kokkona; Furcht, Leo T.; Wohlhueter, Robert M.; Tsilibary, Effie-Photini C

doi:10.2337/diab.39.7.807

Cited by 127 publications

(59 citation statements)

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“…AGE may be produced ex-novo by a slower Maillard reaction or directly derive from these early products through glycoxidation reactions or reactive dicarbonyl fragments generated from free glucose [108]. AGE are toxic products which can modify intracellular proteins, including those involved in the regulation of gene transcription [109], or diffuse outside the cell modifying the extracellular matrix [110], with consequent reduction of the cell-tocell adhesion and vascular dysfunction [65,66], and also modify circulating blood proteins, inducing production of inflammatory cytokines and growth factors [111,112].…”

Section: Pericyte Loss During Dr: Glucose Metabolism Pathwaysmentioning

confidence: 99%

Pericyte Loss in Diabetic Retinopathy: Mechanisms and Consequences

Beltramo

Porta

2013

CMC

257

173

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The onset of diabetic retinopathy is characterized by morphologic alterations of the microvessels, with thickening of the basement membrane, loss of inter-endothelial tight junctions and early and selective loss of pericytes, together with increased vascular permeability, capillary occlusions, microaneurysms and, later, loss of endothelial cells. A key role in the evolution of the disease is played by pericytes, specialized contractile mesenchymal cells of mesodermal origin, that, in capillaries, exert a function similar to smooth muscle cells in larger vessels, regulating vascular tone and perfusion pressure. Thickening of the basement membrane, together with systemic and local hypertension, hyperglycaemia, advanced glycation end-product formation and hypoxia, may disrupt the tight link between pericytes and EC causing pericyte apoptosis, while endothelium, deprived of proliferation control, can give rise to new vessels.Pericyte dropout has great consequences on capillary remodelling and may cause the first abnormalities of the diabetic eye which can be observed clinically. Hyperglycaemia and local hypertension are known to be a direct cause of pericyte apoptosis and dropout, and intracellular biochemical pathways of the glucose metabolites have been explored. However, the exact mechanisms are not yet fully understood and need further clarification in order to develop new effective drugs for the prevention of retinopathy.4

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Section: Pericyte Loss During Dr: Glucose Metabolism Pathwaysmentioning

confidence: 99%

Pericyte Loss in Diabetic Retinopathy: Mechanisms and Consequences

Beltramo

Porta

2013

CMC

257

173

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“…The Schiff base that is formed undergoes Amadori rearrangement and can then condense with an adjacent ketoamine adduct or amino acid side chain to form an irreversible crosslink product (5). Several proteins, including isolated tIV and LM, undergo structural and functional changes after glucose incorporation and/ or ensuing protein crosslinking (6)(7)(8)(9). However, the effect of NEG on the structural integrity of whole BM has not been addressed so far.…”

Section: Introductionmentioning

confidence: 99%

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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“…Extracellular matrix components such as type IV collagen and laminin undergo marked structural changes following glycation [2,3]. The observed alterations might influence the interaction of these components with other basement membrane elements such as Alterations in the density of HS-PG in glomerular basement membrane and the vascular wall are thought to play a role in the development of both glomerular and systemic permeability changes in diabetes [4,5].…”

Section: -14]mentioning

confidence: 99%

mentioning

confidence: 99%

Aminoguanidine reduces regional albumin clearance but not urinary albumin excretion in streptozotocin-diabetic rats

et al. 1994

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Summary Advanced glycation end-product-formation is thought to play a role in the development of diabetic angiopathy. By altering the structure of different extracellular matrix components advanced glycation endproducts might affect vascular and glomerular permeability. In this study we investigated the effect of treatment with an inhibitor of advanced glycation endproduct-formation, aminoguanidine, on vascular permeability and the development of albuminuria in streptozotocin-induced diabetic rats. Male Wistar Rp rats were randomized into a control group, a diabetic group, and an aminoguanidine-treated diabetic group. After 8 weeks, 24-h urine collections were taken and rats were implanted with an arterial and a venous catheter. Mean arterial blood pressure was determined by intra-arterial measurement. Regional albumin clearances were assessed in the eye, ileum, lung, skeletal muscle and skin using an isotope technique. Mean arterial pressure in the diabetic group was significantly lower in the control and aminoguanidine-treated groups (p < 0.02). Regional albumin clearances were significantly increased in all tissues of diabetic rats compared to control rats (p < 0.05). Aminoguanidine treatment of diabetic rats resulted in a significant decrease of regional albumin clearance in all tissues except the lung (p < 0.05, lung p = 0.07). The development of albuminuria in diabetic rats however, was not affected by aminoguanidine. [Diabetologia (1994) 37: 10-14]Key words Diabetes mellitus, rat, advanced glycation end-products, aminoguanidine, vascular permeability, albuminuria.The formation of advanced glycation end-products (AGEs) on long-lived macromolecules has been implicated in the aetiology of diabetic angiopathy. Numerous reports have shown that AGE-formation can alter the function of several systems that are involved in cardiovascular homeostasis [1].Extracellular matrix components such as type IV collagen and laminin undergo marked structural changes following glycation [2,3]. The observed alterations might influence the interaction of these components with other basement membrane elements such as Alterations in the density of HS-PG in glomerular basement membrane and the vascular wall are thought to play a role in the development of both glomerular and systemic permeability changes in diabetes [4,5]. Increases in vascular permeability and increase in urinary albumin excretion have been shown to develop simultaneously in both clinical and experimental diabetes [6][7][8][9].Aminoguanidine, a nucleophilic hydrazine compound, prevents the formation of AGEs [10]. This drug has been shown to decrease albuminuria in spontaneously hypertensive diabetic rats [11]. In addition, experiments in a skin-chamber model suggest that it can reduce the increased vascular permeability induced by hyperglycaemia [12]. We hypothesized that a beneficial effect of aminoguanidine would also imply reduction of increased regional albumin clearance in other organs. Therefore, in this study we assessed the effects of aminoguanidine treatm...

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Laminin Alterations After In Vitro Nonenzymatic Glycosylation

Cited by 127 publications

References 0 publications

Pericyte Loss in Diabetic Retinopathy: Mechanisms and Consequences

Pericyte Loss in Diabetic Retinopathy: Mechanisms and Consequences

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

Aminoguanidine reduces regional albumin clearance but not urinary albumin excretion in streptozotocin-diabetic rats

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