Les sphingolipides : vecteurs d’agents pathogènes et cause de maladies génétiques

Les sphingolipides (SPL) sont des molécules ubiquitaires indispensables au maintien et au développement des organismes vivants. Ils ne sont pas répartis uniformément le long de la membrane mais regroupés sous forme de microdomaines lipidiques appelés rafts. On a longtemps pensé que les SPL avaient uniquement un rôle structural. On sait maintenant qu’ils jouent aussi un rôle de récepteur et de seconds messagers (intervenant dans des fonctions majeures de la vie cellulaire) et que de nombreuses maladies génétiques (sphingolipidoses) s’expliquent par un dysfonctionnement de leur métabolisme. Après un rappel des propriétés structurales des sphingolipides, cet article fait le point sur les relations entre leur rôle de récepteur et l’entrée d’agents pathogènes dans la cellule ainsi que sur les mécanismes pathologiques des sphingolipidoses.Sphingolipids are present in all eukaryotic cells and share a sphingoid base : sphingosine. They were first discovered in 1884 and for a long time they were thought to participate to membrane structure only. Recently it has been established that they are mainly located in particular areas of the membrane called rafts which are signalling platforms. It has also been demonstrated that sphingolipids are receptors and second messengers. They play a crucial role in cellular functioning and are necessary to maintenance and developing of living organisms. However due to their receptor properties, they are also gateway for penetration of pathogenic agents such as virus (Ebola, HIV) or toxins (botulinium, tetanus). These agents first bind to glycosphingolipids or proteins mainly located in rafts. The complex so formed is required for the crossing of the membrane by the pathogenic agent. Sphingolipids metabolism is regulated by numerous enzymes. A failure in the activity of one of them induces an accumulation of sphingolipids known as sphingolipidoses. These are genetic diseases having severe consequences for the survival of the organism. The precise mechanisms of the sphingolipidoses are still mainly unknown which explains why few therapeutic strategies are available. These particular properties of lipids rafts and sphingolipids explain why a growing number of studies in the medical and scientific fields are devoted to them

Neuronal Conduction of Excitation without Action Potentials Based on Ceramide Production

International audienceBACKGROUND: Action potentials are the classic mechanism by which neurons convey a state of excitation throughout their length, leading, after synaptic transmission, to the activation of other neurons and consequently to network functioning. Using an in vitro integrated model, we found previously that peripheral networks in the autonomic nervous system can organise an unconventional regulatory reflex of the digestive tract motility without action potentials. METHODOLOGY/PRINCIPAL FINDINGS: In this report, we used combined neuropharmacological and biochemical approaches to elucidate some steps of the mechanism that conveys excitation along the nerves fibres without action potentials. This mechanism requires the production of ceramide in membrane lipid rafts, which triggers in the cytoplasm an increase in intracellular calcium concentration, followed by activation of a neuronal nitric oxide synthase leading to local production of nitric oxide, and then to guanosine cyclic monophosphate. This sequence of second messengers is activated in cascade from rafts to rafts to ensure conduction of the excitation along the nerve fibres. CONCLUSIONS/SIGNIFICANCE: Our results indicate that second messengers are involved in neuronal conduction of excitation without action potentials. This mechanism represents the first evidence-to our knowledge-that excitation is carried along nerves independently of electrical signals. This unexpected ceramide-based conduction of excitation without action potentials along the autonomic nerve fibres opens up new prospects in our understanding of neuronal functioning

Pectin structure and particle size modify carotenoid bioaccessibility and uptake by Caco-2 cells in citrus juices vs. concentrates

International audienceCitrus pectin is known to influence carotenoid bioaccessibility and absorption in humans, but limited attention has been given to the influence of pectin structure related to the particle size from differentially processed citrus food matrices. In this context, this study aims to investigate the nutritional health benefits of an innovative Citrus clementina concentrate, which is a new citrus-based food made by cross-flow microfiltration. This concentrated citrus-based food was selectively enriched 8-fold in β-cryptoxanthin (43–55 μg g−1) and β-carotene (6–9 μg g−1) as well as 6-fold in pectin (376–462 mg per 100 g). The bioaccessibility of pro-vitamin A carotenoids from commercial and fresh clementina juices versus their concentrates was assessed, including the intestinal carotenoid uptake by Caco-2 cells. Differences in particles size and pectin status resulted in a 7-fold increase in the bioaccessibility of carotenoids in industrial products versus fresh products while limiting their cellular uptake in correlation with larger micelle sizes (10.6 nm and 6.82 nm for industrial and fresh concentrates, respectively). Overall, the highest carotenoid bioaccessibility from industrial concentrate was sufficient to offset the lower carotenoid intestinal uptake related to micelle size. This study highlights that the structure of pectins, more specifically their degree of methoxylation, favors carotenoid bioaccessibility but impairs the intestinal absorption of carotenoids from citrus concentrates

Organisation de la membrane de la bordure en brosse de l'intestin en rafts lipidique - caractérisation protéomique

To assess intestinal lipid rafts functions through the characterization of their protein markers, we have isolated lipid rafts of rat mucosa either from the total membrane or purified brush border membrane (BBM) by sucrose gradient fractionation after detergent treatment. In both membrane preparations, the floating fractions (4-5) were enriched in cholesterol, ganglioside GM1, and N aminopeptidase (NAP) known as intestinal lipid rafts markers. Based on MALDI-TOF/MS identification and simultaneous detection by immunoblotting, 12 proteins from the BBM cleared from contaminants were selected as rafts markers. These proteins include several signaling/trafficking proteins belonging to the G-protein family and the annexins as well as glycosylphosphatidylinositol (GPI)-anchored proteins. Remarkably GP2, previously described as the pancreatic granule GPI-anchored protein, was found in intestinal lipid rafts. The proteomic strategy assayed on the intestine leads to the characterization of known (NAP, alkaline phosphatase, dipeptidyl aminopeptidase, annexin II, and galectin-4) and new (GP2, annexins IV and XIIIb, Gaq, Ga11, glutamate receptor, and GPCR 7) lipid rafts protein markers. Together our results indicate that some digestive enzymes, trafficking and signaling proteins may be functionally distributed in the intestinal lipid rafts.AIX-MARSEILLE3-BU Sc.St Jérô (130552102) / SudocSudocFranceF

Phytochemical Composition and Antioxidant Activity of Fermented Moringa oleifera Leaf Powder

International audienceThe aim of this study was to determine the effects of lactic fermentation of Moringa oleifera leaf powder at young and mature stage of development. This is to improve the organoleptic quality of Moringa oleifera leaf powder. The work was performed in the laboratory of high School of Engineering of La Reunion. The fermentation was performed by Lactobacillus plantarum (DSM 2601) and Weissella cibaria (27A) inoculated at 10 6 CFU / g. The fermentation was performed at 25°C over 5 days. An acidification of fermented products (4 < final pH < 5), a high protein content in mature leaves fermented over 120 hours (T120-Ma), or over 48 h (T48-Ma), by Weissella cibaria, a high protein content in mature leaves fermented over 120 h (T120-Ma) and in young leaves fermented over 120 h (T120-I) by Lactobacillus plantarum was observed. The results of ANOVA on fermentation by Weissella cibaria (27A) and Lactobacillus plantarum (DMS 2601) on the nutritional leaves of Moringa oleifera, showed there was no significant effect on the α=0,05 fermentation times and stage of leaves maturity for contents of reducing sugar and proteins. But there is a significant effect of fermentation and maturation stage leaves on the pH of the product threshold at α=0.05. The fermentation by Lactobacillus plantarum (DMS 2601) showed there was an effect of the fermentation time on the content of phenolic compounds. Principal component Original Research Article Nirina et al.; EJNFS, 7(1): 77-83, 2017; Article no.EJNFS.2017.004 78 analysis (PCA) showed that there is a negative correlation between the protein content and the content of phenolic compounds. By the fermentation process, the organoleptic characteristics of the Moringa oleifera leaves powders whose color is to be improved, which is an asset in the process of incorporation of Moringa oleifera. Lactic fermentation of Moringa oleifera leaves is a method of increasing protein intake of the food and the fight against PEM target populations

Physicochemical and biochemical characterization of ripening injujube (#Ziziphus mauritiana# Lamk) fruits from two accessions grown in Guadeloupe

International audienceJujube fruits (Ziziphus mauritiana Lamk) from two accessions grown in Guadeloupe were harvested andsampled at five ripening stages, from green to reddish-brown in colour. Their physiological character-istics were then investigated. Ascorbic acid increased with ripening until stage 4, to 463 mg/100 g and168 mg/100 g dry weight, for cultivars P3 and P5, respectively. Likewise, ethylene production increaseduntil stage 4, to 121 \ₗ/kg/h and 116 \ₗ/kg/h, for cultivars P3 and P5, respectively. High and transientsucrose accumulation was observed during ripening of P3 fruits, concomitantly with low and constantglucose and fructose contents. P5 fruits also accumulated sucrose transiently but at a lower level than P3fruits, with a marked decrease at the end of ripening. In contrast to P3 fruit, glucose and fructose accu-mulated continuously to high levels during P5 fruit ripening. These data suggested differential sucrosemetabolism during ripening of these fruits. Postharvest treatments with 1-MCP and acetylene were alsoperformed on the three first ripening stages of both cultivars P3 and P5. On the basis of the findings, wediscuss the climacteric behaviour of the P3 and P5 ripening process. (Résumé d'auteur) AD -; CIRAD-PERSYST-UMR Qualisud (FRA); CIRAD-PERSYST-UMR Qualisud (GLP); Université de la Réunion (REU); CIRAD-PERSYST-UMR Qualisud (FRA); CIRAD-PERSYST-UMR Qualisud (GLP

Metabolomic and Lipidomic Analysis of Serum Samples following Curcuma longa Extract Supplementation in High-Fructose and Saturated Fat Fed Rats

International audienceWe explored, using nuclear magnetic resonance (NMR) metabolomics and fatty acids profiling, the effects of a common nutritional complement, Curcuma longa, at a nutritionally relevant dose with human use, administered in conjunction with an unbalanced diet. Indeed, traditional food supplements have been long used to counter metabolic impairments induced by unbalanced diets. Here, rats were fed either a standard diet, a high level of fructose and saturated fatty acid (HFS) diet, a diet common to western countries and that certainly contributes to the epidemic of insulin resistance (IR) syndrome, or a HFS diet with a Curcuma longa extract (1% of curcuminoids in the extract) for ten weeks. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) on the serum NMR profiles and fatty acid composition (determined by GC/MS) showed a clear discrimination between HFS groups and controls. This discrimination involved metabolites such as glucose, amino acids, pyruvate, creatine, phosphocholine/glycerophosphocholine, ketone bodies and gly-coproteins as well as an increase of monounsaturated fatty acids (MUFAs) and a decrease of n-6 and n-3 polyunsaturated fatty acids (PUFAs). Although the administration of Curcuma longa did not prevent the observed increase of glucose, triglycerides, cholesterol and insulin levels, discriminating metabolites were observed between groups fed HFS alone or with addition of a Curcuma longa extract, namely some MUFA and n-3 PUFA, glycoproteins, glutamine, and methanol, suggesting that curcuminoids may act respectively on the fatty acid metabolism, the hexosamine biosynthesis pathway and alcohol oxidation. Curcuma longa extract supplementation appears to be beneficial in these metabolic pathways in rats. This metabolomic approach highlights important serum metabolites that could help in understanding further the metabolic mechanisms leading to IR

Growth and carcass attributes of growing Creole kids according to experimental infection level and type of diet

International audienceIn the tropics one of the major constraints to goat production is infection by gastrointestinal nematodes (GIN). One promising alternative to chemotherapy is the improvement of host nutrition. The aim of this study was to assess the effects of infection and supplementation on packed cell volume (PCV), average daily gain (ADG) and carcass quality in growing Creole kids. Sixty male goats were reared indoors following a 2 × 3 factorial design: two experimental infection levels, (infected (I) and non-infected (NI)) and three diets D (G, kids were fed exclusively with tropical forages; B, kids were supplemented with dried and crushed banana and C, kids were supplemented with commercial pellets). Faecal egg counts did not vary among I groups (on average 2,200 ω/g). The PCV and ADG were improved (P < 0.001) for NI vs. I animals. There was a D effect (P < 0.001) and no I × D interaction was observed. There was no significant effect of GIN on the main carcass data, except the weights of liver, white offal and abdominal fat, which increased slightly in I compared with NI goats (P < 0.05). All carcass data increased significantly with the addition of supplement in the diet (P < 0.001), except for carcass-cut proportions. Meat physical parameters were degraded when I kids received low N diets (B or G) with higher lightness and water loss than in the C groups. Given that GIN affect the animal’s N metabolism it is recommended to avoid the use of unbalanced diet such as those banana-based. Further research is necessary to assess the nutrition × parasitism interactions on physiological features and carcass quality of Creole goats