Specific Uptake of Tumor Necrosis Factor-α Is Involved in Growth Control of Trypanosoma brucei

Trypanosoma brucei is lysed by tumor necrosis factor-α (TNF-α) in a dose-dependent way, involving specific binding of the cytokine to a trypanosomal glycoprotein present in the flagellar pocket of the parasite. TNF-α–gold particles are endocytosed via coated pits and vesicles and are directed towards lysosome-like digestive organelles. The specific uptake of the cytokine by the parasite results in a developmentally regulated loss of osmoregulatory capacity. TNF-α specific lysis is prevented when lysis assays are performed at a temperature <26°C, despite uptake of the cytokine. Inhibition of lysis is also observed when a lysosomotropic agent is added during the first 2 h of incubation. Both monomorphic and pleomorphic trypanosomes are lysed but only when isolated during the peak of parasitaemia. Lysis is not observed with early infection stage parasites or procyclic (insect-specific) forms. Anti– TNF-α treatment of T. brucei-infected mice reveals a dramatic increase in parasitaemia in the blood circulation, the spleen, the lymph nodes, and the peritoneal cavity. These data suggest that in the mammalian host, TNF-α is involved in the growth control of T. brucei

Control of Mitochondrial Membrane Permeabilization by Adenine Nucleotide Translocator Interacting with HIV-1 Viral Protein R and Bcl-2

Viral protein R (Vpr), an apoptogenic accessory protein encoded by HIV-1, induces mitochondrial membrane permeabilization (MMP) via a specific interaction with the permeability transition pore complex, which comprises the voltage-dependent anion channel (VDAC) in the outer membrane (OM) and the adenine nucleotide translocator (ANT) in the inner membrane. Here, we demonstrate that a synthetic Vpr-derived peptide (Vpr52-96) specifically binds to the intermembrane face of the ANT with an affinity in the nanomolar range. Taking advantage of this specific interaction, we determined the role of ANT in the control of MMP. In planar lipid bilayers, Vpr52-96 and purified ANT cooperatively form large conductance channels. This cooperative channel formation relies on a direct protein–protein interaction since it is abolished by the addition of a peptide corresponding to the Vpr binding site of ANT. When added to isolated mitochondria, Vpr52-96 uncouples the respiratory chain and induces a rapid inner MMP to protons and NADH. This inner MMP precedes outer MMP to cytochrome c. Vpr52-96–induced matrix swelling and inner MMP both are prevented by preincubation of purified mitochondria with recombinant Bcl-2 protein. In contrast to König's polyanion (PA10), a specific inhibitor of the VDAC, Bcl-2 fails to prevent Vpr52-96 from crossing the mitochondrial OM. Rather, Bcl-2 reduces the ANT–Vpr interaction, as determined by affinity purification and plasmon resonance studies. Concomitantly, Bcl-2 suppresses channel formation by the ANT–Vpr complex in synthetic membranes. In conclusion, both Vpr and Bcl-2 modulate MMP through a direct interaction with ANT

Cationized ferritin binding and internalization during in vitro aging of mouse embryonic fibroblasts

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Étude au microscope électronique de l'action de l'hydroxyurée sur les embryons. II. Embryons d'amphibiens

Pleurodeles waltlii eggs were treated with hydroxyurea (1 mg/ml or 2 mg/ml) for 22 h, from the 2 cells stage onwards. Controls (aged blastulae) and hydroxyurea treated embryos (blocked at the morula-young blastula stage) were studied with the electron microscope. The nuclei of normal blastulae contain many nucleolar corpuscles (about 1 μ in diameter) of fibrillar structure, or larger nucleoli of partially granular structure. In hydroxyurea treated embryos, the nucleolar components have segregated and the chromatin is condensed in a coarse network. Granules similar to cytoplasmic glycogen particles can be seen in the nuclear sap; this abnormal localization is the result of mitotic abnormalities. The alterations observed in hydroxyurea treated eggs are consistent with the hypothesis of a direct action of this substance on DNA itself. © 1968.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

A study of the effects of ethidium bromide on the ultrastructure of sea urchin embryos

This study describes the ultrastructural changes which result from treatment of sea urchin embryos (Paracentrotus lividus) with ethidium bromide, particularly in: the chromatin (formation of a network of materials of various densities or clumping), the nucleoli (no typical granular region), the mitochondria (swelling, reduction in the number of cristae, appearance of numerous dense granules or a dense mass in the matrix) and the heavy bodies (enlargement and prolonged existence). The experimental conditions were as follows: Treatment with different doses from ten minutes before fertilization continued for 90 minutes afterwards. Treatment with a high dose (100 μg/ml) for three hours at the young blastula stage. Treatment with a low dose (15 μg/ml) for 48 hours from fertilization onwards. Active nucleo‐cytoplasmic exchange visibly occurs across the nuclear membrane of control embryos throughout development: emission of multivesicular ergastoplasmic sacs into the cytoplasm up to the blastula stage and formation of ergastoplasmic diverticulae by its outer leaflet from the gastrula stage onwards. These signs of nuclear membrane activity are also observed in embryos treated with ethidium bromide. Copyright © 1971 Wiley‐Liss, Inc. A Wiley CompanySCOPUS: ar.jinfo:eu-repo/semantics/publishe

Étude ultrastructurale des embryons normaux et des hybrides létaux entre Echinodermes

Normal (Paracentrotus ♀ x Paracentrotus ♂) and lethal hybrid (Paracentrotus ♀ x Arbacia ♂) sea urchin embryos were fixed at the time of blocking (late bastulae) and 6 h later, and studied with the electron microscope. At the time of the arrest of development the hybrid blastulae lack a typical ergastoplasm and contain many vesicles dispersed throughout the cytoplasm. The situation becomes normal 6 h later. These results are discussed in relation to current knowledge of nucleic acid metabolism in lethal hybrids. © 1968.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Mise en evidence au microscope électronique de polysomes actifs dans des lobes polaires isolés d'Ilyanassa

Polar lobes of Ilyanassa embryos, isolated at the trefoil stage, were incubated for 2 h in the presence of a mixture of 3H-phenylalanine and 3H-leucine. This material has been studied by high-resolution sutoradiography. The activity is mainly associated with granule aggregates with a polysomal appearance. Silver grains are also often localized over mitochondria. The results are discussed in relation to hypothesies on the morphogenetic function of the polar lobe. © 1969.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Contribution à l'étude du métabolisme des oocytes d'échinodermes

Doctorat en Sciencesinfo:eu-repo/semantics/nonPublishe

Étude au microscope électronique de l'action de l'hydroxyurée sur les embryons. I. Embryons d'oursins

Paracentrotus lividus eggs were treated with hydroxyurea (1 mg/ml) for 5 h 15 min, immediately after fertilization. This inhibitor of DNA synthesis blocks cleavage at the 4-8 blastomere stage. Both treated and control embryos (morulae) were fixed for an ultrastructural study. The nuclei of the controls contain nucleolar corpuscles (about 0.5 μ in diameter) whose fibrillar component can be condensed into granules. The nuclei of the hydroxyurea treated eggs contain many spherules (about 1.5 μ in diameter) of condensed fibrillar structure. The perivitelline space of the hydroxyurea treated embryos contains polysaccharide granules clumped together or arranged in small chains. At the morula stage, these polysaccharide granules are no longer seen in the perivitelline space, but occur in some of the yolk platelets or in vacuoles localized in a concavity of these platelets. The alterations observed in hydroxyurea treated eggs are consistent with the hypothesis of a direct action of this substance on DNA itself. © 1968.SCOPUS: ar.jinfo:eu-repo/semantics/publishe