Long chain scorpion toxins (made of 60 to 70 amino acids) acting on voltage-gated sodium channels in excitable cells are responsible for human envenomation, and comprise a-toxins that inhibit current inactivation p-toxins, modify the activation process. These may be further divided according their pharmacological activities. Thus, highly active mammals or insects, as well α like distinguished within α-toxin class. The β-toxin class includes and, a separate group, excitatory depressant...

The massive uptake of compatible osmolytes such as betaine, taurine, and myo-inositol is a protective response shared by all eukaryotes exposed to hypertonic stress. Their accumulation results mostly from the expression specific transporters triggered transcriptional factor NFAT5/TonEBP. This allows recovery cell volume without increasing intracellular ionic strength. In this study we consider assembly dissociation mRNA stress granules (SGs) in hypertonic-stressed cells role osmolytes....

To date, the translation of Au (III) complexes into chemotherapeutic agents has been hindered by their low stability under physiological conditions, a crucial parameter in drug development. In this study, we report an innovative four-step synthesis stable (III)-doxorubicin (DOX) complex, acting as key constitutive component doxorubicin-loaded PEG-coated nanoparticles (DOX IN-PEG-AuNPs). For therapeutic purposes, such AuNPs were then functionalized with anti-Kv11.1 polyclonal antibody (pAb),...

Connexins are structurally related transmembrane proteins that assemble to form gap junction channels involved in the mediation of intercellular communication. It has been shown intracellular tail connexin43 (Cx43) interacts with tubulin and microtubules putative impacts on its own trafficking, activity channel communication, interference specific growth factor signal transduction cascades. We demonstrate here microtubule binding Cx43 is mainly driven by a short region 26 amino acid residues...

κ-Conotoxin PVIIA from the venom of Conus purpurascens is first cone snail toxin that was described to block potassium channels. We synthesized chemically this and showed its disulfide bridge pattern similar those ω- δ-conotoxins. κ-conotoxin competes with radioactive α-dendrotoxin for binding rat brain synaptosomes, confirming capacity bind channels; however, it behaves as a weak competitor. The three-dimensional structure PVIIA, elucidated by NMR spectroscopy molecular modeling, comprises...

Acute-on-chronic liver failure is characterized by acute deterioration of function in patients with compensated or decompensated, but stable, cirrhosis. However, there no accurate definition acute-on-chronic and physicians often use this term to describe different clinical entities. Metabolomics investigates metabolic changes biological systems identifies the biomarkers profiles. Our study assessed metabolomic profile serum using proton nuclear magnetic resonance ((1)H-NMR) spectroscopy...

Background Glioma cells not only secrete high levels of vascular endothelial growth factor (VEGF) but also express VEGF receptors (VEGFR), supporting the existence an autocrine loop. The direct impact on glioma metabolism drugs targeting pathway, such as Bevacizumab (Bev) or VEGFR Tyrosine Kinase Inhibitor (TKI), is poorly known. Material and Methods U87 were treated with Bev SU1498, a selective VEGFR2 TKI. expression was checked FACS flow cytometry Quantitative Real-Time PCR. secretion into...

The study of the membrane insertion translocation domain diphtheria toxin deepens our insight into interactions between proteins and membranes. During cell intoxication, this undergoes a change from soluble folded state at alkaline pH to functional membrane-inserted acid pH. We found that hydrophobic electrostatic occur in sequential manner during insertion. first step involves by C-terminal region. This is because pH-induced formation molten globule specialized for binding membrane....

Phox homology (PX) domains have been recently identified in a number of different proteins and are involved various cellular functions such as vacuolar targeting membrane protein trafficking. It was shown that these modules about 130 amino acids specifically binding to phosphoinositides this interaction is crucial for their function. The yeast genome contains 17 PX domain proteins. One these, Grd19p, the localization late Golgi DPAP A Kex2p. Grd19p consists with 30 extra residues at...

The C-terminal region of tubulin is involved in multiple aspects the regulation microtubule assembly. To elucidate molecular mechanisms this regulation, we study here, using different approaches, interaction Tau, spermine, and calcium, three representative partners region, with a peptide composed last 42 residues α1a-tubulin. results show that their binding involves overlapping amino acid stretches region: 421-441 for 430-432 444-451 421-443 calcium. Isothermal titration calorimetry, NMR,...

Microtubules are cytoskeletal components involved in multiple cell functions such as mitosis, motility, or intracellular traffic. In vivo, these polymers made of alphabeta-tubulin nucleate mostly from the centrosome to establish interphasic microtubule network or, during mitotic spindle. Centrosomal P4.1-associated protein (CPAP; also named CENPJ) is a centrosomal assembly centrioles and important for function. This contains microtubule-destabilizing region referred PN2-3. Here we decrypt...

Periodontitis is characterized by the loss of supporting tissues teeth in an inflammatory-infectious context. The diagnosis relies on clinical and X-ray examination. Unfortunately, signs tissue destruction occur late disease progression. Therefore, it mandatory to identify reliable biomarkers facilitate a better earlier management this disease. To end, saliva represents promising fluid for identification as metabolomic fingerprints. present study used high-resolution 1H-nuclear magnetic...

Septic shock is the most severe phase of sepsis and associated with high rates mortality. However, early stage prediction septic outcomes remains difficult. Metabolomic techniques have emerged as a promising tool for improving prognosis. Orthogonal projections to latent structures-discriminant analysis (OPLS-DA) models separating serum metabolomes survivors from those non-survivors were established samples obtained at intensive care unit (ICU) admission (H0) 24 h later (H24). For 51 patients...

Sarcoidosis is a systemic inflammatory immune disease characterised by non-caseating granulomas. Its course can vary from benign to very severe, requiring appropriate treatment. Few biomarkers are available monitor the management of these patients and identify those at risk poor prognosis. Given nature sarcoidosis, we hypothesised that analysis urine metabolites could provide valuable for severe disease. We designed comparative metabolomics in consecutive cohort 37 well phenotyped patients,...

This paper emphasizes the synthesis of novel hybrid drug nanoparticles (Hyb-D-AuNPs) based on gold-temozolomide (TMZ) complexes combined with gemcitabine (GEM) and decitabine (DAC) to improve efficiency reduce resistance U87 malignant glial cells against TMZ. All products were evaluated by several spectroscopic techniques (Raman, UV-Vis) transmission electron microscopy (TEM). Besides, for therapeutic purposes, effect these cell proliferation toxicity was evaluated, which clearly showed a...

Abstract We have determined the three‐dimensional structure of potassium channel inhibitor HsTX1, using nuclear magnetic resonance and molecular modeling. This protein belongs to scorpion short toxin family, which essentially contains blockers 29 39 amino acids three disulfide bridges. It is highly active on voltage‐gated Kv1.3 channels. Furthermore, it has particularity possess a fourth bridge. show that HsTX1 fold similar three‐disulfide‐bridged toxins conserves hydrophobic core found in...

Owing to preferential electrostatic adsorption of multivalent cations on highly anionic surfaces, natural polyamines and especially quadrivalent spermine can be considered as potential regulators the complex dynamical properties MTs (microtubules). Indeed, C-terminal tails tubulin display many negative residues in a row which should enable formation correlated liquid-like phase counterions its surface. Although it is known that polyamine promote MT assembly vitro, little about relevance this...

Long-term endurance exercise severely affects metabolism in both human and animal athletes resulting serious risk of metabolic disorders during or after competition. Young horses (up to 6 years old) can compete races up 90 km despite limited scientific knowledge energetic responses long distance these animals. The hypothesis this study was that there would be a strong effect on the metabolomic profiles young response different from more experienced horses. Metabolomic profiling is powerful...

Background: The prevention and early screening of PCa is highly dependent on the identification new biomarkers. In this study, we investigated whether plasma metabolic profiles from healthy males provide novel biomarkers associated with future risk PCa. Methods: Using Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) cohort, identified samples collected 146 cases up to 13 years prior diagnosis 272 matched controls. Plasma were characterized using ultra-high-performance liquid...

Diabetes mellitus is a widely prevalent chronic disease, and effective treatments for it remain limited. Allicin has anti-diabetic effect, however, the detailed mechanism not been well investigated. The diabetic rats were treated with allicin 6 weeks, then fecal samples, serum tissues collected measurement of gut microbiota (GM), bile acids (BAs) other indexes. decreased blood glucose levels, lipid alleviated hepatic deposition rats. Simultaneously, changed composition GM increased secondary...

Microtubules are major cytoskeletal components involved in numerous cellular functions such as mitosis, cell motility, or intracellular traffic. These cylindrical polymers of αβ-tubulin assemble a closely regulated dynamic manner. We have shown that the stathmin family proteins sequester tubulin nonpolymerizable ternary complex, through their stathmin-like domains (SLD) and thus contribute to regulation microtubule dynamics. demonstrate here short peptides derived from N-terminal part SLDs...

We report the surface-mediated polymerization of FtsZ protein, prokaryote homologue tubulin, by AFM. protein can form filaments on mica whereas bulk concentration is orders magnitude lower than critical concentration. Surface favored a local increase in and requires high mobility proteins surface. To generalize to other cytoskeleton we also show that initiate formation tubulin protofilaments. This study particular interest for studying cytoskeletal dynamics AFM but surface autoassembly...