L-Lys, not only as an inhibitor of glycation but also as a chemical chaperone and a protein chaperone inducer, causes effective changes in many parameters of the model animals. However, it is not enough to achieve complete improvement.
A decrease in complications in diabetic rats after hot-tub therapy is shown here. An increase in the extracellular Hsp70 level due to HTT was observed. This increase may serve to protect the structure of proteins (e.g. preventing AGE formation), and the observed beneficial effects may be related to it.
Diabetes mellitus has been classified as a conformational disease because of changes induced in the structure and function of proteins due to hyperglycemia. In this study, we investigated the effect of high-dose and long-term use of acetyl salicylic acid (ASA) on the streptozotocin-induced diabetic rats as a model of type I diabetes, with consideration on the structure and/or function of proteins. The N-[methylnitrosocarbamoyl]-D-glucosamine (streptozotocin)-induced diabetic rats together with the normal rats were studied for 5 months with and without receiving 100 mg/kg ASA in drinking water. All rats were investigated from different aspects such as heat shock protein (HSP) 70 level, serum glucose and insulin concentration, advanced glycated end product (AGE) and glycated hemoglobin (HbA1c) formation, lipid profile, high-density lipoprotein (HDL) functionality (paraoxonase1 and lecithin cholesterol acyltransferase activities), and the antioxidant system. In addition, the in vitro effect of ASA on the structure of albumin as a model protein was studied in the presence of glucose by spectroscopic techniques such as fluorometry and circular dichroism. The results show that ASA therapy causes a decrease in the glucose level and AGE and HbA1c formation, improves the lipid profile, HDL functionality, and the antioxidant capacity, induces serum HSP70, and overall decreases mortality of diabetic rats in comparison with the group without treatment. The conformation of glycated bovine serum albumin is different from the native form, and ASA retains the conformation of this protein similar to the native. The improving effect of ASA on diabetic rats is mostly due to its role as a chemopreventive agent in the structural conservation and protection of proteins involved in diabetes pathogenesis.
Nonenzymatic glycation of biomacromolecules occurs due to the diabetes mellitus and ageing. A number of small molecules, known as chemical chaperones, stabilize protein conformation against thermal and chemically induced denaturation. These compounds are including: polyamines (e.g. spermine and spermidine), amino acids (e.g. lysine) and polyols (e.g. glycerol). In this study the effect of spermidine (Spd), spermine (Spm), and glycerol on glycation, structure and function of lysozyme (LZ), as an extra-cellular protein, by different techniques is investigated. LZ is incubated with or without glucose (50 or 100 mM) in the absence or presence of Spd/Spm/glycerol at 37 °C up to 16 weeks. All the observed changes of glycated-LZ in comparison with the native protein, including: increased fluorescence emission, alteration in the secondary and tertiary structure, and reduced electrophoretic mobility- indicate its structural changes that are accompanied with its reduced activity. Glucose in the presence or absence of Spd induces the protein dimerization, but glucose plus Spm induces its trimmerization. In contrast, glycerol inhibits the LZ glycation and prevents the large changes on its structure and function. Glucose binds lysine residues, decreases the protein positive charges and induces some alterations in its structure and activity. Polyamines also directly bind to LZ, increase its positive charges and hence induce more glycation; more conformational changes, oligomerization and its inactivation in the presence of glucose, but glycerol affect the protein environment and preserve protein from these harmful effects.
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