Oxydation de phospholipides polyinsaturés dans des systèmes membranaires biomimétiques (effets de molécules amphiphiles et d'enzymes antioxydantes)

Le stress oxydant résulte de l'altération par des radicaux libres de nombreuses cibles cellulaires. De nombreuses maladies ainsi que les phénomènes liés au vieillissement découlent de ces attaques radicalaires. Afin de mieux cerner les processus physiopathologiques liés au stress oxydant, nous nous sommes intéressés à l'oxydation lipidique des membranes dans un système membranaire biomimétique : les monocouches de Langmuir. Les études ont porté sur l'oxydation d'un phospholipide polyinsaturé, la 1,2-dilinoléoyl-sn-glycéro-3-phosphocholine (DLiPC). L'oxydation de la DLiPC, réalisée par exposition à un rayonnement UV à 254 nm, se traduit par une diminution de l'aire moléculaire. Après irradiation, les isothermes de compression et le module d'élasticité de surface révèlent l'apparition de nouvelles espèces moléculaires à l'interface air-eau. Grâce à ce système d'analyse, nous avons testé les propriétés d'agents anti-oxydants naturels (plasmalogène et cholestérol) et d'antioxydants synthétiques (dérivés de l' -phényl-N-tert-butylnitrone). En déterminant le temps de latence, précédent la diminution d'aire moléculaire, ainsi que l'amplitude de cette diminution, l'effet protecteur de ces molécules a pu être quantifié. Nous avons ensuite comparé les propriétés interfaciales des deux enzymes impliquées dans le stress oxydant : les peroxydases à glutathion (GPx) de type 1 et 4. Les différences de comportement observées pour les deux GPx indiquent une affinité différente selon la nature du phospholipide insaturé à l'interface air-eau pour la GPx-4 ce qui n'est pas le cas pour la GPx-1. Nous avons également caractérisé les propriétés interfaciales des adduits de Michaël qui résultent de la modification de phospholipides par des produits d'oxydation.LYON1-BU.Sciences (692662101) / SudocSudocFranceF

Étude des propriétés interfaciales de polyphénols modèles (compréhension des mécanismes d'action au niveau membranaire)

COMPIEGNE-BU (601592101) / SudocSudocFranceF

Nanoscale analysis of supported lipid bilayers using atomic force microscopy.

During the past 15years, 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. Here, we survey recent progress made in the area

Modèles membranaires biomimétiques pour l'incorporation du cytochrome bc1 des chaînes de transfert d'électrons photosynthétiques de Rhodobacter sphaeroides

COMPIEGNE-BU (601592101) / SudocSudocFranceF

Interaction de molécules antipaludiques avec des systèmes membranaires biomimétiques

COMPIEGNE-BU (601592101) / SudocSudocFranceF

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

International audienc

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

International audienceThe work reported herein deals with the evaluation of the antioxidant properties of bitailed amphiphilic ␣-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. the water soluble AAPH and the Fenton reaction, and the antioxidant evaluation was carried out using two biomimetic systems, namely Langmuir monolayers and large unilamellar vesicles. Measurement of the molecular area and the membrane fluidity of pure nitrone monolayers before and after UV-irradiation demonstrated the better stability and antioxidant properties of B 17 PBN, the derivative with two C 17 H 35 alkyl chains, compared to its analogue B 11 PBN with two C 11 H 23 alkyl chains. At only 5% molar ratio of nitrone in mixed DLoPC/nitrone monolayers, a complete inhibition of the molecular area decrease was observed for B 17 PBN whereas B 11 PBN showed lower protection. The oxidation of mixed DLoPC/nitrones large unilamellar vesicles in the presence of free radicals arising from AAPH decomposition or Fenton reaction was assessed by measuring lipid conjugated dienes and thiobarbituric acid reactive substances on the whole series of nitrone, i.e. C 11-, C 13-, C 15-and C 17-based compounds. Compared to the saturated 1,2-dimyristoyl-sn-glycero-3-phosphocholine, all bitailed amphiphilic nitrones were able to decrease conjugated dienes and TBARS in both oxidative paradigms, demonstrating therefore antioxidant property. The inhibition of phospholipids oxidation was increased when increasing the concentration of nitrone with the two B 11 PBN and B 13 PBN derivatives exhibiting higher potency. This study underlines the importance in the choice of a model membrane system when evaluating the potency of antioxidants against lipid oxidation

Plasmalogens protect unsaturated lipids against UV-induced oxidation in monolayer

AbstractOxidative stress results from the attack by free radicals of several cellular targets (proteins, DNA and lipids). The cell equilibrium is a direct consequence of the pro-/antioxidant balance. In order to understand the physiological processes involved in oxidative stress, we followed oxidation of unsaturated lipids using a biomimetic system: Langmuir monolayers. The oxidation mode chosen was UV-irradiation and the lipid model was a polyunsaturated phospholipid: 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC). The monomolecular film technique was used to measure membrane rheology before and after UV-irradiation. We showed that the UV-irradiation of a DLPC monomolecular film led to a molecular area and surface elasticity modulus decrease that attests to the apparition of new molecular species at the air–water interface. The antioxidant effect of a synthetic plasmalogen (1-O-(1′-(Z)-hexadecenyl)-2-O-oleoyl-sn-glycero-3-phosphocholine or PPLMOPE) was tested on the oxidation of DLPC. Indeed, for about 25% mol PPLMOPE in mixed DLPC/PPLMOPE monolayers, a complete inhibition of the molecular area and the surface elasticity modulus decreases was observed in our experimental conditions. Lower PPLMOPE quantities delayed but did not prevent the DLPC oxidation in mixed monolayers

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

International audiencePolyunsaturated 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. We evidenced a relationship between the structure and the anti-oxidant efficiency as aglycone compounds were significantly more efficient (p < 0.05) than glucoside compounds. In addition, our results revealed that aglycone lignans spontaneously penetrated the membrane contrary to aglycone hydroxycinnamic acids. To conclude, the comparison of the antioxidant efficiencies revealed that membrane inserted compounds better inhibited lipid oxidation than non-inserted compounds