Atorvastatin treatment softens human red blood cells: An optical tweezers study

Optical tweezers are proven indispensable single-cell micro-manipulation and mechanical phenotyping tools. In this study, we have used optical tweezers for measuring the viscoelastic properties of human red blood cells (RBCs). Comparison of the viscoelastic features of the healthy fresh and atorvastatin treated cells revealed that the drug softens the cells. Using a simple modeling approach, we proposed a molecular model that explains the drug-induced softening of the RBC membrane. Our results suggest that direct interactions between the drug and cytoskeletal components underlie the drug-induced softening of the cells. © 2018 Optical Society of America

Atorvastatin treatment softens human red blood cells: An optical tweezers study

Optical tweezers are proven indispensable single-cell micro-manipulation and mechanical phenotyping tools. In this study, we have used optical tweezers for measuring the viscoelastic properties of human red blood cells (RBCs). Comparison of the viscoelastic features of the healthy fresh and atorvastatin treated cells revealed that the drug softens the cells. Using a simple modeling approach, we proposed a molecular model that explains the drug-induced softening of the RBC membrane. Our results suggest that direct interactions between the drug and cytoskeletal components underlie the drug-induced softening of the cells. © 2018 Optical Society of America

Inhibition study on insulin fibrillation and cytotoxicity by paclitaxel

Alzheimer, a neurodegenerative disease, and a large variety of pathologic conditions are associated with a form of protein aggregation known as amyloid fibrils. Since fibrils and prefibrillar intermediates are cytotoxic, numerous attempts have been made to inhibit fibrillation process as a therapeutic strategy. Peptides, surfactants and aromatic small molecules have been used as fibrillation inhibitors. Here we studied the effects of paclitaxel, a polyphenol with a high tendency for interaction with proteins, on fibrillation of insulin as a model protein. The effects of paclitaxel on insulin fibrillation were determined by Thioflavin T fluorescence, Congo red absorbance, circular dichroism and atomic force microscopy. These studies indicated that paclitaxel considerably hindered nucleation, and therefore, fibrillation of insulin in a dose-dependant manner. The isothermal titration calorimetry studies showed that the interaction between paclitaxel and insulin was spontaneous. In addition, the van der Waal's interactions and hydrogen bonds were prominent forces contributing to this interaction. Computational results using molecular dynamic simulations and docking studies revealed that paclitaxel diminished the polarity of insulin dimer and electrostatic interactions by increasing the hydrophobicity of its dimer state. Furthermore, paclitaxel reduced disrupting effects of insulin fibrils on PC12 cell's neurite outgrowth and complexity, and enhanced their survival. © 2014 The Authors 2014

SPECTROSCOPIC STUDIES OF INHIBITION OF CALMODULIN ACTIVITY BY SOME DRUGS

The effect of four inhibitors on calmalulin (CuM) were studied by a ftuorescence and ultraviolet techniques. Four compounds IN - ( 6 - aminohexyt) 5-chloro - I - napthalenesulphonamide] (W-7), 1 - [ bis - (4 - chtorophenyt) methyl] - 3 - [2, 4-dichloro - β - ( 2 , 4 - dichlorobenzyloxyl) phenethyt] imidazolium chloride (R24571), trifluoperazine (TFP) , thiodiphenylamide chloride (TDPAC) showed inhibitory effect on bovine brain phosphodiesterase (PDE) induced by CaM. The concentration of inhibitors producing 50% inhibition of of Ca 2+ / CaM activity activity (IC50) and the Hill coefficient were correlating closely between the methods, Ki's and thermodynamic parameters for these interactions were estimated

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. © 2013 Elsevier B.V

Curcumin mitigates the fibrillation of human serum albumin and diminishes the formation of reactive oxygen species

The formation of amyloid fibrils are thought to contribute to pathogenesis of many amyloids associated human diseases. Here the impact of curcumin on amyloid formation of human serum albumin (HSA) was studied. Incubation of HSA at 68°C under physiologic pH led to amyloid fibril formation. Thioflavin T (ThT) fluorescence was used for determination of amyloid fibril formation. Atomic force microscopy experiments indicated different fibril structure of HSA incubated with or without curcumin. The monitoring of the changes in reactive oxygen species (ROS) levels upon incubation of curcumin with HSA showed a significant decrease in ROS levels. Similar experiments were also carried out in the presence of aflatoxin M1 (AFM1) and lead (Pb) ions. Our results indicated that AFM1 and Pb ions promote the fibrillation of HSA and accelerate ROS production, which were inhibited in the presence of curcumin. Thus, curcumin mitigates protein fibrillation activity and diminishes ROS generation. © 2015 Bentham Science Publishers

Thermal reversibility and disaggregation of human serum albumin upon incubation with 3-β hydroxybutyrate: A proposed mechanism for thiol reaction

Thermal inactivation of proteins is a main challenge in food technology and medicine. The 3-β-hydroxybutyrate (3BHB) is the most abundant ketone body with a carboxyl group. Its concentration increases during fasting, prolonged exercise, and in diabetic patients. In this work, human serum albumin (HSA) was incubated with 3BHB for 7, 14, 21, and 35 days under physiological conditions. The thermal reversibility and thermal aggregation of HSA upon incubation with 3BHB were determined by differential scanning calorimetry and free amine content assay. These results indicated that 3BHB binds the lysine residues of HSA through nucleophilic attack leading to formation of covalent bonds. The calorimetric results showed that the modification of lysine residues by 3BHB resulted in partial unfolding of HSA compared to the modification of thiol group of Cys34, which is surrounded by other amino acid side chains. Since thermal aggregation of HSA is related to Cys34, its modification caused a decrease in thermal aggregation and an increase in thermal reversibility of modified HSA. © 2014 Akadémiai Kiadó

Beneficial protective role of endogenous lactic acid bacteria against mycotic contamination of honeybee beebread

International audienceThe purpose of this article is to reveal the role of the lactic acid bacteria (LAB) in the beebread transformation/preservation, biochemical properties of 25 honeybee endogenous Lstrains, particularly: antifungal, proteolytic, and amylolytic activities putatively expressed in the beebread environment have been studied. Seventeen fungal strains isolated from beebread samples were identified and checked for their ability to grow on simulated beebread substrate (SBS) and then used to study mycotic propagation in the presence of LAB. Fungal strains identified as Aspergillus niger (Po1), Candida sp. (BB01), and Z. rouxii (BB02) were able to grow on SBS. Their growth was partly inhibited when co-cultured with the endogenous honeybee Lstrains studied. No proteolytic or amylolytic activities of the studied Lwere detected using pollen, casein starch based media as substrates. These findings suggest that some honeybee Lsymbionts are involved in maintaining a safe microbiological state in the host honeybee colonies by inhibiting beebread mycotic contaminations, starch, and protein predigestion in beebread by Lis less probable. Honeybee endogenous Luse pollen as a growth substrate and in the same time restricts fungal propagation, thus showing host beneficial action preserving larval food. This study also can have an impact on development of novel methods of pollen preservation and its processing as a food ingredient