End-stage renal disease and diabetes catalyze the formation of a pentose-derived crosslink from aging human collagen.

Abstract

Structure elucidation of a specific fluorophore from the aging extracellular matrix revealed the presence of a protein crosslink formed through nonenzymatic glycosylation of lysine and arginine residues. The unexpected finding that a pentose instead of a hexose is involved in the crosslinking process suggested that the crosslink, named pentosidine, might provide insight into abnormalities of pentose metabolism in aging and disease. This hypothesis was investigated by quantitating pentosidine in hydrolysates of 103 human skin specimens obtained randomly at autopsy.Pentosidine level was found to increase exponentially from 5 to 75 pmol/mg collagen over lifespan (r = 0.86, P < 0.001). A three-to tenfold increase was noted in insulin-dependent diabetic and nondiabetic subjects with severe end-stage renal disease requiring hemodialysis (P < 0.001). Moderately elevated levels were also noted in some very old subjects, some subjects with non-insulin dependent diabetes, and two subjects with cystic fibrosis and diabetes. The cause of the abnormal pentose metabolism in these conditions is unknown but may relate to hemolysis, impaired pentose excretion, cellular stress, and accelerated breakdown of ribonucleotides.Thus, pentosidine emerges as a useful tool for assessment of previously unrecognized disorders of pentose metabolism in aging and disease. Its presence in red blood cells and plasma proteins suggests that it might be used as a measure of integrated pentosemia in analogy to glycohemoglobin for the assessment of cumulative glycemia. (J. Clin. Invest. 1990. 85:380-384.) advanced glycosylation -arginine -imidazopyridine -lysine * Maillard reaction Introduction Recently this laboratory reported the presence of skin collagen-linked fluorescence that accumulates during normal aging and that was increased in 98% of insulin-dependent diabetic subjects (1). There was an overall correlation between collagen-linked fluorescence and severity of retinopathy, arterial and joint stiffness, and systolic blood pressure. The analogy between the fluorescence properties of diabetic skin and those of collagen incubated with glucose suggested that advanced glycosylation (Maillard) reaction had formed at a higher rate in

Advanced glycation end-products: a review

“…The lack of internal standards leaves assays open to error which require a high degree of accuracy and reproducability for each sample run. Currently the most common methods used for detection are HPLC [16,88], ELISA [79,95] and immunohistochemistry [96]. Recently, a monoclonal antibody which recognises CML, called 6D12, has become commercially available [97,98].…”

“…Histopathological studies have shown AGE accumulation in a variety of tissue types, including coronary atheroma, renal cortex, mesangium and glomerular basement membrane [12], as well as the dermal layer [13], amyloid plaques in Alzheimer's disease [14], cartilage in rheumatoid arthritis [15], cardiac muscle, lung and liver [16].…”

Advanced glycation end products and their receptors co-localise in rat organs susceptible to diabetic microvascular injury

“…Long-lived proteins such as collagen are modified by prolonged exposure to glucose resulting in AGE formation. In diabetes, a state of chronic hyperglycaemia, the accumulation of AGEs is accelerated [19]. Proteins that have undergone advanced glycation have a characteristic fluorescence which may be used for quantitation of AGEs [7].…”

Matrix metalloproteinase activities and their relationship with collagen remodelling in tendon pathology

“…Pentosidine, an advanced glycation end-product (AGE), has been used as a marker of the biological age of the collagen network in a wide range of tissues such as dura mater (Sell and Monnier, 1989;Monnier et al, 1992), skin (Monnier et al, 1992;Sell and Monnier, 1990;Sell et al, 1993), lens-proteins (Dyer et al, 1991) and cartilage (Bank et al, 1998;Verzijl et al, 2000a). It accumulates in a linear fashion with age in the short head of biceps brachii, a tendon that is rarely affected by pathology (Bank et al, 1999).…”