Interplay Between Membrane Lipid Peroxidation and Photoproduct Formation in the Ultraviolet A-Induced Phototoxicity of Vemurafenib in Skin Keratinocytes

International audienceAccording to some authors, the phototoxic response to ultraviolet A (UVA) of patients treated with vemurafenib (VB) may involve VB metabolites. However, the production of singlet oxygen and free radicals and photoproduct formation upon UVA light absorption by the lipophilic VB have been demonstrated. This work is aimed at determining the contribution of reactive oxygen species (ROS), lipid photoperoxidation, and VB photochemistry in the UVA-induced photocytotoxicity in NCTC 2544 keratinocytes. The potent membrane lipid peroxidation effectiveness of VB-photosensitization has been proved by the observation of an effective photohemolysis accompanied by thiobarbituric reactive substances (TBARS) formation in 2% red blood cell (RBC) suspensions. Photohemolysis is inhibited by human serum albumin (HSA) that binds VB and by the antioxidants 2,6-di-tert-butyl-4-methylphenol and Trolox. These data on RBC suggest that VB is readily incorporated in cell membranes and provide clues for understanding the UVA-induced VB-photosensitization of keratinocytes. In keratinocytes, ROS and TBARS formation with 10 mM VB is inhibited by approximately 40% and 50% by 30 mM Trolox and 50 mM vitamin E, respectively, but the light dose-dependent cell survival is unaffected. Whereas cell photokilling depends on the VB concentration, much smaller changes in the lethal doses (LD) than theoretically expected are observed for 25% or 50% cell photokilling when changing absorbed UVA doses and irradiation wavelengths. The lack of antioxidant effect on cell survival and the unexpectedly small LD dependence on absorbed UVA light doses and on irradiation wavelengths strongly suggest that, instead of metabolites, membrane photosensitization and photoproduct formation contribute to the cell photocytotoxicity

Human Foamy Virus Capsid Formation Requires an Interaction Domain in the N Terminus of Gag

Retroviral Gag expression is sufficient for capsid assembly, which occurs through interaction between distinct Gag domains. Human foamy virus (HFV) capsids assemble within the cytoplasm, although their budding, which mainly occurs in the endoplasmic reticulum, requires the presence of homologous Env. Yet little is known about the molecular basis of HFV Gag precursor assembly. Using fusions between HFV Gag and a nuclear reporter protein, we have identified a strong interaction domain in the N terminus of HFV Gag which is predicted to contain a conserved coiled-coil motif. Deletion within this region in an HFV provirus abolishes viral production through inhibition of capsid assembly

Standard methods for toxicology research in Apis mellifera

Modern agriculture often involves the use of pesticides to protect crops. These substances are harmful to target organisms (pests and pathogens). Nevertheless, they can also damage non-target animals, such as pollinators and entomophagous arthropods. It is obvious that the undesirable side effects of pesticides on the environment should be reduced to a minimum. Western honey bees (Apis mellifera) are very important organisms from an agricultural perspective and are vulnerable to pesticide-induced impacts. They contribute actively to the pollination of cultivated crops and wild vegetation, making food production possible. Of course, since Apis mellifera occupies the same ecological niche as many other species of pollinators, the loss of honey bees caused by environmental pollutants suggests that other insects may experience a similar outcome. Because pesticides can harm honey bees and other pollinators, it is important to register pesticides that are as selective as possible. In this manuscript, we describe a selection of methods used for studying pesticide toxicity/selectiveness towards Apis mellifera. These methods may be used in risk assessment schemes and in scientific research aimed to explain acute and chronic effects of any target compound on Apis mellifera

Économie et société de la fin de la Préhistoire : Actualité de la recherche

Les 7e Rencontres méridionales de Préhistoire récente, tenues à Bron, sur le campus de l'Université Lumière-Lyon 2, les 3 et 4 novembre 2006, ont réuni plus de 150 préhistoriens venus du Sud de la France et des régions alentour. Ces Rencontres biennales représentent le lien majeur de la communauté des chercheurs pour les périodes allant du Mésolithique à l'Âge du Bronze dans la moitié sud de la France. Les Actes présentés ici regroupent 24 contributions réparties en deux sections : l'actualité de la recherche, présentant les principaux résultats des fouilles et programmes récents, et le thème spécifique choisi pour cette session « Économie et société à la fin de la Préhistoire ». Cette thématique large est abordée au fil de 9 contributions très ciblées portant sur les économies de subsistance, de production et d'échange ainsi que sur l'analyse de structures immobilières qui en témoignent, où l'on voit que l'idéel et le matériel ne sont jamais très éloignés dans ces sociétés du passé