Collagen molecules in articular cartilage have an exceptionally long lifetime, which makes them susceptible to the accumulation of advanced glycation end products (AGEs). In fact, in comparison to other collagen-rich tissues, articular cartilage contains relatively high amounts of the AGE pentosidine. To test the hypothesis that this higher AGE accumulation is primarily the result of the slow turnover of cartilage collagen, AGE levels in cartilage and skin collagen were compared with the degree of racemization of aspartic acid (% D-Asp, a measure of the residence time of a protein). AGE (N ⑀ -(carboxymethyl)lysine, N ⑀ -(carboxyethyl)lysine, and pentosidine) and % D-Asp concentrations increased linearly with age in both cartilage and skin collagen (p < 0.0001). The rate of increase in AGEs was greater in cartilage collagen than in skin collagen (p < 0.0001). % D-Asp was also higher in cartilage collagen than in skin collagen (p < 0.0001), indicating that cartilage collagen has a longer residence time in the tissue, and thus a slower turnover, than skin collagen. In both types of collagen, AGE concentrations increased linearly with % D-Asp (p < 0.0005). Interestingly, the slopes of the curves of AGEs versus % D-Asp, i.e. the rates of accumulation of AGEs corrected for turnover, were identical for cartilage and skin collagen. The present study thus provides the first experimental evidence that protein turnover is a major determinant in AGE accumulation in different collagen types. From the age-related increases in % D-Asp the half-life of cartilage collagen was calculated to be 117 years and that of skin collagen 15 years, thereby providing the first reasonable estimates of the half-lives of these collagens.Nonenzymatic glycation is a post-translational modification of proteins in vivo, which is initiated by the spontaneous reaction of sugars with lysine residues in proteins and eventually results in the formation of advanced glycation end products (AGEs), 1 such as N ⑀ -(carboxymethyl)lysine (CML), N ⑀ -(carboxyethyl)lysine (CEL), and pentosidine (1-3). Because AGEs are irreversible chemical modifications of protein, they accumulate with age in long lived proteins such as lens crystallins and tissue collagens (1, 3-9). Because collagen molecules in articular cartilage have an exceptionally long lifetime (Ͼ100 years) (10, 11), they are highly susceptible to the accumulation of AGEs. Indeed, in comparison to other collagen-rich tissues (such as skin), articular cartilage contains relatively high amounts of pentosidine (3, 12). Although differences in AGE levels between different proteins have been attributed to differences in protein turnover rates (3,(12)(13)(14), no quantitative evidence to support this assumption is available.To compare protein turnover rates, information on the residence time of a protein in tissue can be obtained from the racemization of aspartic acid. Amino acids are incorporated into peptides and proteins as the L-enantiomers. During aging, racemization slowly converts the L-form into a race...
Aims/hypothesis We determined whether oxidative damage in collagen is increased in (1) patients with diabetes; (2) patients with diabetic complications; and (3) subjects from the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study, with comparison of subjects from the former standard vs intensive treatment groups 4 years after DCCT completion. Subjects, materials and methods We quantified the early glycation product fructose-lysine, the two AGEs N ɛ -(carboxymethyl)lysine (CML) and pentosidine, and the oxidised amino acid methionine sulphoxide (MetSO) in skin collagen from 96 patients with type 1 diabetes (taken from three groups: DCCT/EDIC patients and clinic patients from South Carolina and Scotland) and from 78 healthy subjects. Results Fructose-lysine was increased in diabetic patients (p<0.0001), both with or without complications (p<0.0001).Controlling for HbA 1c , rates of accumulation of AGEs were higher in diabetic patients than control subjects, regardless of whether the former had complications (CML and pentosidine given as log e [pentosidine]) or not (CML only) (all p<0.0001). MetSO (log e [MetSO]) also accumulated more rapidly in diabetic patients with complications than in controls (p<0.0001), but rates were similar in patients without complications and controls. For all three products, rates of accumulation with age were significantly higher in diabetic patients with complications than in those without (all p<0.0001). At 4 years after the end of the DCCT, no differences were found between the previous DCCT management groups for fructose-lysine, AGEs or MetSO. Conclusions/interpretation The findings suggest that in type 1 diabetic patients enhanced oxidative damage to collagen is associated with the presence of vascular complications.
Denitrification rates in aquatic sediments from three sites upland of high salinity estuaries were measured to compare nitrate (NO−3) removal by sediment bacteria. The study sites included two blackwater creeks that drain to coastal inlets (one in an undeveloped coastal forest and the second in a suburban residential development) and drainage pond on a golf course. Two to 20 mmol NO−3 kg−1 soil was added to microcosms and the acetylene block technique was used to estimate denitrification. Nitrate, nitrous oxide (N2O) and ammonium (NH+4) concentrations were monitored over time. The rate and efficiency of denitrification was low at the 2 mmol NO−3 kg−1 addition and increased proportionally with NO−3 added. Across all treatments, the golf course sediment that received consistent N inputs in situ had the most rapid and greatest N2O production, while the salt marsh in the undeveloped area had the least. The NH+4 concentrations remained constant and low (2 mmol N kg−1) except at the undeveloped, forested Oyster Creek (8 mmol NH+4‐N kg−1). In most cases, the majority of NO−3 removal did not occur until 24 to 48 h of incubation, regardless of N2O production. During typical low‐ and no‐flow periods, this time frame may be adequate for slow diffusion of nutrients and removal of NO−3 prior to transport to coastal estuaries or ground water, particularly at the golf course site. However, this time frame may not be adequate during rapid water and nutrient transport due to severe storm events typical of this region.
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