Dataset Information

Non-enzymic glycation of fibrous collagen: reaction products of glucose and ribose.

ABSTRACT: Non-enzymic glycation of collagen involves a series of complex reactions ultimately leading to the formation of intermolecular cross-links resulting in changes in its physical properties. During analysis for the fluorescent cross-link pentosidine we identified the presence of an additional component (Cmpd K) in both glucose and ribose incubations. Cmpd K was formed more quickly than pentosidine in glucose incubations and more slowly than pentosidine in ribose incubations. Cmpd K represented 45% of the total fluorescence compared with 15% for pentosidine in glucose incubations and 25% of the total fluorescence compared with 30% for pentosidine in the ribose incubations. Cmpd K is not an artefact of in vitro incubations, as it was shown to be present in dermal tissue from diabetic patients. Subsequent high-resolution h.p.l.c. analysis of glucose-incubated collagen revealed Cmpd K comprise two components (K1 and K2). Further, a similar analysis of Cmpd K from the ribose incubations revealed two different components (K3 and K4). These differences indicate alternative mechanisms for the reactions of glucose and ribose with collagen. The amounts of these fluorescent components and the pentosidine cross-link determined for both glucose and ribose glycation were found to be far too low (about one pentosidine molecules per 200 collagen molecules after 6 months incubation with glucose) to account for the extensive cross-linking responsible for the changes in physical properties, suggesting that a further additional series of cross-links are formed. We have analysed the non-fluorescent high-molecular-mass components and identified a new component that increases with time of in vitro incubation and is present in the skin of diabetic patients. This component is present in sufficient quantities (estimated at one cross-link per two collagen molecules) to account for the changes in physical properties occurring in vitro.

SUBMITTER: Bailey AJ

PROVIDER: S-EPMC1136373 | biostudies-other | 1995 Jan

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:The immune system provides host protection to infection with pathogenic organisms, while at the same time providing tolerance upon exposure to harmless antigens. Thus, an impaired immune function is associated with increased susceptibility to infections with increased disease severity and thereby necessitating the therapeutic use of antibiotics. Livestock performance and feed efficiency, in addition to their health status, are dependent on the microbial load of their gut, the barrier function of the intestinal epithelium and the activity of the mucosal immune system, all of which can be modulated by dietary components. The majority of feeds that are consumed in pets and livestock have been processed. Processing promotes a non-enzymatic reaction between proteins and sugars called Maillard reaction (MR). Maillard reaction products (MRPs) and advanced Maillard reaction products (AGEs) determine taste, smell, and color of many food products therefore the MR is highly relevant for the feed industry. MRPs interact with different types of immune receptors, including the receptor for advanced glycation end products (RAGE) and immunomodulatory potential of feed proteins can be modified by Maillard reaction. This MR has become an important concern since MRPs/AGEs have been shown to contribute to increasing prevalence of diet-related chronic inflammatory states in the gut with negative health consequences and performance. The immunomodulatory effects of dietary MRPs and AGEs in livestock and pet animals are far less well-described, but widely considered to be similar to the relevant concepts and mechanisms obtained in the human field. This review will highlight immunological mechanisms underlying initiation of the innate and adaptive immune responses by MRPs/AGEs present in animal feeds, which are currently not completely understood. Bridging this knowledge gap, and taking advantage of progress in the human field, will significantly improve nutritional quality of feed and increase the prevention of diet-mediated inflammation in animals.

Project description:Background Although diabetes attenuates abdominal aortic aneurysms (AAAs), the mechanisms by which diabetes suppresses AAAs remain incompletely understood. Accumulation of advanced glycation end- (AGEs) reduces extracellular matrix (ECM) degradation in diabetes. Because ECM degradation is critical for AAA pathogenesis, we investigated whether AGEs mediate experimental AAA suppression in diabetes by blocking AGE formation or disrupting AGE-ECM cross-linking using small molecule inhibitors. Methods and Results Male C57BL/6J mice were treated with streptozotocin and intra-aortic elastase infusion to induce diabetes and experimental AAAs, respectively. Aminoguanidine (AGE formation inhibitor, 200 mg/kg), alagebrium (AGE-ECM cross-linking disrupter, 20 mg/kg), or vehicle was administered daily to mice from the last day following streptozotocin injection. AAAs were assessed via serial aortic diameter measurements, histopathology, and in vitro medial elastolysis assays. Treatment with aminoguanidine, not alagebrium, diminished AGEs in diabetic AAAs. Treatment with both inhibitors enhanced aortic enlargement in diabetic mice as compared with vehicle treatment. Neither enhanced AAA enlargement in nondiabetic mice. AAA enhancement in diabetic mice by aminoguanidine or alagebrium treatment promoted elastin degradation, smooth muscle cell depletion, mural macrophage accumulation, and neoangiogenesis without affecting matrix metalloproteinases, C-C motif chemokine ligand 2, or serum glucose concentration. Additionally, treatment with both inhibitors reversed suppression of diabetic aortic medial elastolysis by porcine pancreatic elastase in vitro. Conclusions Inhibiting AGE formation or AGE-ECM cross-linking enhances experimental AAAs in diabetes. These findings support the hypothesis that AGEs attenuate experimental AAAs in diabetes. These findings underscore the potential translational value of enhanced ECM cross-linking as an inhibitory strategy for early AAA disease.

Project description:Glucose-lysine based Maillard reaction products (MRPs) are introduced to the human body via food ingestion or are synthesized in vivo. Depending on reaction conditions, they represent a mixture of compounds with diverse chemical structures and physiological properties. MRPs may also be a potential nutrient source for Salmonella, a major foodborne gastrointestinal pathogen. This study was designed to determine the growth and transcriptional responses of S. Typhimurium LT2 to MRPs generated at low water activity to simulate the reaction occurring during food processing and storage. Maillard reactions between N-α-acetyl-lysine and glucose were varied in time (4, 23, and 143 h) to generate sub-samples with prevailing Amadori compound, advanced glycation end products (AGEs), or melanoidines respectively. The addition of MRP up to 5 mg mL-1 to defined media with 0.4% glucose had no effect on S. Typhimurium LT2 growth. In media, where the MRP sub-samples (4 and 23 h) served as the only carbon source, MRP assimilation by S. Typhimurium LT2 was observed as secondary logarithmic growth phases (0.063 h-1 and 0.072 h-1) after the growth on glucose available in the MRP reaction mixtures (0.479 h-1). The MRPs sub-sample with the highest concentration of melanoidines (143 h) also supported S. Typhimurium LT2 growth (0.368 h-1). Of the three MRPs sub-samples, the Amadori compound was the preferred carbon source for S. Typhimurium LT2 as evidenced by its almost complete disappearance (98%). Decreases in AGEs (37%) and melanoidines (15%), when incubated with S. Typhimurium LT2, also occurred. Transcription profiles of the cells grown on the MRPs fractions revealed predominant up-regulation of genes associated with the functional groups of energy metabolism, fatty and phospholipid metabolism, cellular process, and regulatory functions, and general down-regulation of the genes in the groups of amino acid biosynthesis, protein synthesis and transcription, transport and binding proteins, and DNA metabolism. The carbon flow in tricarboxylic acid (TCA) cycle partitioned by the glyoxylate cycle appeared to play an essential role in the assimilation of glucose-lysine-derived MRPs. The high expression level of numerous genes encoding hypothetical proteins or proteins with unknown function suggested the presence of genes whose role in glucose-lysine MRPs catabolism in Salmonella remains to be determined.

Dataset Information

Non-enzymic glycation of fibrous collagen: reaction products of glucose and ribose.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets