Serum and Soleus Metabolomics Signature of Knockout Mice to Identify Potential Biomarkers.

The transcription factor Krüppel-like factor 10 (), also known as Tieg1 for TGFβ (Inducible Early Gene-1) is known to control numerous genes in many cell types that are involved in various key biological processes (differentiation, proliferation, apoptosis, inflammation), including cell metabolism and human disease. In skeletal muscle, particularly in the soleus, deletion of the gene ( KO) resulted in ultrastructure fiber disorganization and mitochondrial metabolism deficiencies, characterized by muscular hypertrophy. To determine the metabolic profile related to loss of expression, we analyzed blood and soleus tissue using UHPLC-Mass Spectrometry.

Krüppel-like factor 10 regulates the contractile properties of skeletal muscle fibers in mice.

Introduction/aims: Klf10 is a member of the Krüppel-like family of transcription factors, which is implicated in mediating muscle structure (fiber size, organization of the sarcomere), muscle metabolic activity (respiratory chain), and passive force. The aim of this study was to further characterize the roles of Klf10 in the contractile properties of skeletal muscle fibers.

Methods: Fifty-two single fibers were extracted from female wild-type (WT) and Klf10 knockout (KO) oxidative (soleus) and glycolytic (extensor digitorum longus [EDL]) skinned muscles.

First step to the improvement of the blood brain barrier passage of atazanavir encapsulated in sustainable bioorganic vesicles.

The blood - brain barrier (BBB) prevents the majority of therapeutic drugs from reaching the brain following intravenous or oral administration. In this context, polymer nanoparticles are a promising alternative to bypass the BBB and carry drugs to brain cells. Amphiphilic cyclodextrins can form self-assemblies whose nanoparticles have a 100-nm-diameter range and are thus able to encapsulate drugs for controlled release.

Nitrone-Trolox conjugate as an inhibitor of lipid oxidation: Towards synergistic antioxidant effects.

Free radical scavengers like α-phenyl-N-tert-butylnitrone (PBN) and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) have been widely used as protective agents in various biomimetic and biological models. A series of three amphiphilic Trolox and PBN derivatives have been designed by adding to those molecules a perfluorinated chain as well as a sugar group in order to render them amphiphilic. In this work, we have studied the interactions between these derivatives and lipid membranes to understand how they influence their ability to prevent membrane lipid oxidation.

Flax phenolic compounds as inhibitors of lipid oxidation: Elucidation of their mechanisms of action.

Polyunsaturated fatty acids are particularly sensitive to the damages due to reactive oxygen species and lipid oxidation has been reported to be involved in the degradation of food as well as in the early stages of several diseases. Our objective was to study the mechanisms of action of flax (Linum usitatissimum) phenolic compounds to prevent membrane lipid oxidation. To do so, several biophysical techniques (oxidative stress, surface tension, fluorescence spectroscopy and HPLC) were used to investigate the ability of the compounds to prevent lipid oxidation and to interact with membranes.

Cholesterol-nitrone conjugates as protective agents against lipid oxidation: A model membrane study.

Free radical scavengers such as α-phenyl-N-tert-butylnitrone (PBN) have been widely used as protective agents in several biological models. We recently designed two PBN derivatives by adding a cholesterol moiety to the parent nitrone to increase its lipophilicity. In addition to the cholesterol, a sugar group was also grafted to enhance the hydrophilic properties at the same time.

Synthesis, iron(III) complexation properties, molecular dynamics simulations and P. aeruginosa siderophore-like activity of two pyoverdine analogs.

P. aeruginosa ranks among the top five organisms causing nosocomial infections. Among the many novel strategies for developing new therapeutics against infection, targeting iron uptake mechanism seems promising as P.

Antioxidant and Membrane Binding Properties of Serotonin Protect Lipids from Oxidation.

Serotonin (5-hydroxytryptamine, 5-HT) is a well-known neurotransmitter that is involved in a growing number of functions in peripheral tissues. Recent studies have shown nonpharmacological functions of 5-HT linked to its chemical properties. Indeed, it was reported that 5-HT may, on the one hand, bind lipid membranes and, on the other hand, protect red blood cells through a mechanism independent of its specific receptors.

Hematin loses its membranotropic activity upon oligomerization into malaria pigment.

Malaria is an infectious disease caused by Plasmodium type parasites transmitted by the bites of infected female anopheles mosquitoes. The malaria parasite multiplies in red blood cells where it degrades hemoglobin. This degradation of hemoglobin proteins releases hematin, an iron-containing porphyrin, which provokes membrane disruption and lysis.

Topological effects and binding modes operating with multivalent iminosugar-based glycoclusters and mannosidases.

Multivalent iminosugars have been recently explored for glycosidase inhibition. Affinity enhancements due to multivalency have been reported for specific targets, which are particularly appealing when a gain in enzyme selectivity is achieved but raise the question of the binding mode operating with this new class of inhibitors. Here we describe the development of a set of tetra- and octavalent iminosugar probes with specific topologies and an assessment of their binding affinities toward a panel of glycosidases including the Jack Bean α-mannosidase (JBαMan) and the biologically relevant class II α-mannosidases from Drosophila melanogaster belonging to glycohydrolase family 38, namely Golgi α-mannosidase ManIIb (GM) and lysosomal α-mannosidase LManII (LM).

PBN derived amphiphilic spin-traps. II/Study of their antioxidant properties in biomimetic membranes.

The work reported herein deals with the evaluation of the antioxidant properties of bitailed amphiphilic α-phenyl-N-tert-butylnitrone derivatives (BPBNs) towards oxidation of an unsaturated lipid, the 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLoPC). Oxidation was induced either by UV light irradiation or radical initiators, i.e.

Probing the nature of the cluster effect observed with synthetic multivalent galactosides and peanut agglutinin lectin.

We designed a set of multi-galactosides with valencies ranging from one to seven and different spacer-arm lengths. The compounds display a high structural homology for a strict assessment of multivalent phenomena. The multimers were first evaluated by an enzyme-linked lectin assay (ELLA) toward the peanut agglutinin (PNA).

Atomic force microscopy of model lipid membranes.

Supported lipid bilayers (SLBs) are biomimetic model systems that are now widely used to address the biophysical and biochemical properties of biological membranes. Two main methods are usually employed to form SLBs: the transfer of two successive monolayers by Langmuir-Blodgett or Langmuir-Schaefer techniques, and the fusion of preformed lipid vesicles. The transfer of lipid films on flat solid substrates offers the possibility to apply a wide range of surface analytical techniques that are very sensitive.

Titanium dioxide nanoparticles disturb the fibronectin-mediated adhesion and spreading of pre-osteoblastic cells.

In the context of rapid development of nanoparticles (NPs) for industrial applications, the question of their toxicity and biological effects must be considered. In this work, we have assessed the influence of titanium dioxide NPs on the adhesion and spreading of MC-3T3 pre-osteoblasts by using a cell subclone that does not produce its own extracellular matrix. Petri dishes were coated with the important adhesion protein fibronectin (Fn).

Preosteoblasts and fibroblasts respond differently to anatase titanium dioxide nanoparticles: a cytotoxicity and inflammation study.

There is a bundle of proofs suggesting that some industrial nanoparticles (NPs) can provoke diseases and pollute the environment durably. However, these issues still remain controversial. In the biomedical field, TiO(2) NPs were recently proposed to serve as fillers in polymeric materials to improve bone prostheses and scaffolds.

The natural antioxidant rosmarinic acid spontaneously penetrates membranes to inhibit lipid peroxidation in situ.

Exogenous molecules from dietary sources such as polyphenols are very efficient in preventing the alteration of lipid membranes by oxidative stress. Among the polyphenols, we have chosen to study rosmarinic acid (RA). We investigated the efficiency of RA in preventing lipid peroxidation and in interacting with lipids.

The potent antimalarial peptide cyclosporin A induces the aggregation and permeabilization of sphingomyelin-rich membranes.

Cyclosporin A (CsA) is a hydrophobic peptide drug produced by the fungus Tolypocladium inflatum. CsA is commonly used as an immunosuppressive drug, but it also has antimalarial activity. The immunosuppressive activity of CsA is clearly due to its association with specific proteins of immune cells such as cyclophilins.

Cytochrome c provokes the weakening of zwitterionic membranes as measured by force spectroscopy.

Cytochrome c (cyt c) is a small soluble protein from the intermembrane space of mitochondria. This protein is essential because it transfers electrons between two membrane complexes of the respiratory chain. In fact, during this transfer, the positively charged amino-acid residues surrounding the heme in the protein structure allow the cyt c to interact properly with the anionic part of other molecules: mainly the cardiolipin-rich membrane of mitochondria and respiratory complexes.

Preparation of an electrochemical biosensor based on lipid membranes in nanoporous alumina.

Model lipid bilayers are versatile tools to investigate the molecular processes occurring at the membrane level. Among the model membranes, substrate supported bilayers have attracted much interest because they are robust and they can be investigated by powerful surface sensitive techniques such as electrochemical measurements. In a biosensor, lipid films can be used not only as a support for the biological sensing elements but also as sensing elements themselves to detect molecules that are able to alter the structure and the properties of biomembranes.

Activity of immobilised rat hepatic microsomal CYP2E1 using alumina membrane as a support.

Porous alumina membranes are attractive materials for the construction of biosensors and also have utility for the production of immobilised enzyme bioreactors. Microsomes from rat liver were adsorbed onto alumina membrane activated by silane. Microsomal membranes were pumped through the channels where they became immobilised by binding to amine groups on the surface of the alumina membrane.

Cytochrome c interaction with neutral lipid membranes: influence of lipid packing and protein charges.

The interaction of cytochrome c (cyt c) with fluid/gel neutral supported lipid membranes was investigated by time-lapse atomic force microscopy (AFM). AFM revealed the random formation of depressed areas in fluid membranes promoted by cyt c. These depressions corresponded to the desorption of fluid bilayer patches induced by cyt c.

The potent antimalarial drug cyclosporin A preferentially destabilizes sphingomyelin-rich membranes.

Cyclosporin A (CsA) is a hydrophobic cyclic peptide produced by a fungus. CsA is widely used as an immunosuppressive agent to inhibit the rejection of transplanted organs. CsA also exhibits an antiparasitic activity against Plasmodium, the microorganism responsible for malaria disease.

Nanoscale analysis of supported lipid bilayers using atomic force microscopy.

During the past 15 years, atomic force microscopy (AFM) has opened new opportunities for imaging supported lipid bilayers (SLBs) on the nanoscale. AFM offers a means to visualize the nanoscale structure of SLBs in physiological conditions. A unique feature of AFM is its ability to monitor dynamic events, like bilayer alteration, remodelling or digestion, upon incubation with various external agents such as drugs, detergents, proteins, peptides, nanoparticles, and solvents.

Development of immobilization technique for liver microsomes.

In the present report, physically adsorbed rat liver microsomes were used in order to optimize the immobilization of membrane proteins on solid surfaces for use in biosensing and microreactor applications. Physical adsorption was used to form thin films on solid supports (gold, mica, macroporous aluminum oxide membrane). The characterization of the films was performed by surface plasmon resonance (SPR), atomic force microscopy (AFM) and environmental scanning electron microscopy (ESEM).

Real-time atomic force microscopy reveals cytochrome c-induced alterations in neutral lipid bilayers.

The interaction of cytochrome c (cyt c) with supported lipid membranes was investigated on the nanoscale by real-time atomic force microscopy. Cyt c promoted the formation and the expansion of depressed areas in the fluid parts of the bilayer. When the depressions reached the gel domains, they induced the thickening of their edges.