Antiamyloidogenic Effects of Ellagic Acid on Human Serum Albumin Fibril Formation Induced by Potassium Sorbate and Glucose.

Oxidative stress has the main role in protein conformational changes and consequent direct involvement in different kind of diseases. Potassium sorbate as a widespread industrial preservative and glucose are two important oxidants that can be involved in oxidative stress. In this study the effect of ellagic acid as a phenolic antioxidant on amyloid fibril formation of human serum albumin upon incubation of potassium sorbate and glucose was studied using thioflavin T assay, surface tension, atomic force microscopy, Amadori product, and carbonyl content assays. The thioflavin T assay and atomic force microscopy micrographs demonstrated the antiamyloidogenic effect of ellagic acid on the human serum albumin fibril formation. This antioxidant also had the repair effect on surface tension of the modified human serum albumin (amyloid intermediates), which was destructed, caused by potassium sorbate and glucose. This mechanism takes place because of potent carbonyl stress suppression effect of ellagic acid, which was strengthening by potassium sorbate in the presence and absence of glucose.

Inhibition of fluorescent advanced glycation end products (AGEs) of human serum albumin upon incubation with 3-ß-hydroxybutyrate.

Advanced glycation end products (AGEs), which are the final products of glycation, have a major role in diabetic complication and neurodegenerative disorders. The 3-ß-hydroxybutyrate (3BHB), a ketone body which is produced by the liver, can be detected in increased concentrations in individuals post fasting and prolonged exercises and in diabetic (type I) patients. In this study, the inhibitory effect of 3BHB on AGEs formation by glucose from the human serum albumin (HSA) was studied at physiological conditions after 35 days of incubation, using physical techniques such as circular dichroism and fluorescence spectroscopy, as well as differential scanning calorimetry (DSC). The fluorescence intensity measurements of glycated HSA by glucose (GHSA) in the presence of 3BHB indicate a decrease in AGEs formation. The DSC deconvolution profile results also confirm the protective role of 3BHB on incubated with glucose by preventing the enthalpy reduction of the HSA tail segment, compared with the deconvolution profile seen for incubated with glucose alone. The concentration of 3BHB used in this study is in accordance with the concentration detected in the body of individuals post fasting and prolonged exercises.

Design of neural networks for fast convergence and accuracy: dynamics and control.

A procedure for the design and training of artificial neural networks, used for rapid and efficient controls and dynamics design and analysis for flexible space systems, has been developed. Artificial neural networks are employed, such that once properly trained, they provide a means of evaluating the impact of design changes rapidly. Specifically, two-layer feedforward neural networks are designed to approximate the functional relationship between the component/spacecraft design changes and measures of its performance or nonlinear dynamics of the system/components. A training algorithm, based on statistical sampling theory, is presented, which guarantees that the trained networks provide a designer-specified degree of accuracy in mapping the functional relationship. Within each iteration of this statistical-based algorithm, a sequential design algorithm is used for the design and training of the feedforward network to provide rapid convergence to the network goals. Here, at each sequence a new network is trained to minimize the error of previous network. The proposed method should work for applications wherein an arbitrary large source of training data can be generated. Two numerical examples are performed on a spacecraft application in order to demonstrate the feasibility of the proposed approach.

Potassium sorbate as an AGE activator for human serum albumin in the presence and absence of glucose.

Advanced glycation end products (AGEs) are the predominant intermediates of glycation process, and mediate oxidative stress and complications of diabetes. Potassium sorbate (PS) as a widespread preservative is an oxidative agent and used in different dairy and drug products, which can readily enter biological matrices. Here we studied the PS interference with glycation of human serum albumin (HSA) in the presence of glucose (Glc) using various techniques. These included TNBSA assay, circular dichroism, fluorescence spectroscopy, differential scanning calorimetry (DSC), Th T assay, and atomic force microscopy. Our results indicated that HSA glycation was accelerated in the presence of PS. Furthermore, PS produced AGEs in the absence of glucose. Secondary and tertiary structural changes were also observed in HSA incubated with glucose in the presence or absence of PS through beta-sheet inducing effects. Th T assay demonstrated the role of PS in HSA fibril formation in the presence or absence of glucose. Atomic force microscopy determined different amyloid fibril formation in HSA incubated with PS in the presence or absence of glucose. Together our results indicated that PS has a stimulatory effect on glycation and fibrillation of HSA in the presence or absence of glucose, and could exacerbate complication of diabetes.

Investigation of thermal reversibility and stability of glycated human serum albumin.

Protein glycation, the process by which carbohydrates attach to proteins upon covalent binding, can alter protein thermal reversibility and stability. Protein stability and reversibility have important role in protein behavior and function. Also they are benefit properties for drug produce and protein industrial applications. In this research the thermal reversibility and stability changes in human serum albumin (HSA) were studied upon incubation with glucose (GHSA) under physiological conditions for 21 and 35 days. The thermal reversibility and stability changes in GHSA were evaluated using circular dichroism (CD), UV-vis spectroscopy, fluorescence spectroscopy and differential scanning calorimetry (DSC). Our results showed that the glycation of HSA increased its thermal reversibility and stability, but decreased its conformational entropy compared to fresh native HSA and untreated HSA. Free lysine content assay (TNBSA test) indicated glucose can bind to protein covalently. These alterations were mainly attributed to the formation of crosslink between the lysine residues of HSA upon incubation with glucose.