Comptes rendus des seances de la Societe de biologie et de ses filiales最新文献

Glucocorticoids are physiological molecules that are also extensively used in clinics as anti-inflammatory, immunosuppressive or anti-tumoral agents. Glucocorticoids can induce apoptosis on normal lymphoid cells and play a key role in the physiology of thymic selection. In clinics these molecules are also used for their potencies in inducing apoptosis of malignant lymphoid cells. Glucocorticoids are mediating their effects after binding to an intracellular receptor belonging to the steroid receptor superfamily: the glucocorticoid receptor (GR). Once activated, the GR, can mediate his effects through direct binding on the DNA or via protein/protein interactions with transcription factors. Depending on the type of lymphocytes, the mechanism of apoptosis induced by glucocorticoids fall roughly in two categories: induction of "death genes" by the activated GR (I kappa B, c-jun) or repression of survival factors (AP-1, c-Myc). In the case of thymic selection the mechanism is more subtle depending on the mutual repression of Nur77 and GR.

Apoptosis is a genetically programmed cell death that is required for morphogenesis during embryogenic development and for tissue homeostasis in adult organisms. In most cases, apoptosis involves cytochrome c release from mitochondria. In the cytosol, cytochrome c combines with APAF-1 in the presence of ATP to activate caspase-9 that, in turn, activates effectors caspases such as caspase-3. Bcl-2 and related proteins control cytochrome c release from the mitochondria whereas IAP (for Inhibitor of APoptosis) molecules modulate the activity of caspases. Plasma membrane receptors such as Fas (CD95, APO-1), characterized by a so-called "death domain" in their cytoplasmic domain, can activate the caspase cascade through adaptator molecules such as FADD (Fas-Associated protein with a Death Domain). Dysregulation of the apoptotic machinery plays a role in the pathogenesis of various diseases and molecules involved in cell death pathways are potential therapeutic targets in immunologic, neurologic, cancer, infectious and inflammatory diseases.

Injections of modafinil, a drug able to induce in vertebrates an awakening effect via an effective central alpha 1-adrenergic tone, induce modifications of the amplitude and latency of electroretinograms (ERGs) in the spider Lycosa tarentula, during dark adaptation. Results of experiments are different from one eye type to another as circadian activity rhythms of the retinae also differ. Modafinil induces a decrease of diurnal amplitudes and has no effect on nocturnal amplitudes of ERGs of anterior-lateral eyes; in the case of posterior-median eyes, the amplitudes are increased in daytime as well as at night. Prazosin, antagonist of alpha 1-adrenergic receptors, injected after modafinil, induces a decrease of the amplitudes of ERGs in the same eyes. These results are discussed in relation to the visual activity of this species, both diurnal and nocturnal. The concepts of waking state versus sleep are not precisely characterized in arachnids, so that the effects of modafinil on L. tarentula may not be considered like those described in vertebrates.

Since a few years, many mutations in genes encoding voltage-dependent ion channels have been identified. The related disorders are quoted as "channelopathies". These mutations are responsible for several skeletal muscle, brain, heart or kidney diseases. Abnormal calcium channels genes are responsible for hypokaleamic periodic paralysis (CACNA1S) as well as some forms of ataxia, cerebellar degeneration and migraine (CACNA1A). The preliminary studies of the recently discovered calcium channelopathies are undergoing. Both in vitro and in vivo studies of the diseased genes should help to the understanding of the related pathologies as well as to extend our knowledge of calcium channel function. In addition, autoantibodies against calcium channels are retrieved in some autoimmune diseases, such as Lambert-Eaton myasthenic syndrome (LEMS). Complementary studies are necessary to identify the precise implication of calcium channels in these auto-immune channelopathies.

The hormone-mediated intercellular Ca2+ waves were analyzed in multiplets of rat hepatocytes by video imaging of fura2 fluorescence. These multicellular systems are composed of groups of several cells (doublets to quintuplets) issued from the liver cell plate, a one cell-thick cord of about 20 hepatocytes long between portal and centrolobular veins. When the multiplets were homogeneously bathed with the glycogenolytic agonists vasopressin, noradrenaline, angiotensin II and ATP, they showed highly organized Ca2+ signals. Surprisingly, for a given agonist, the primary rises in intracellular Ca2+ concentration ([Ca2+]i) originated invariably in the same hepatocyte, then was propagated in a sequential manner to the nearest connected cells (cell 2, then 3, cell 4 in a quadruplet, for example). The sequential activation of the cells appeared to be an intrinsic property of multiplets of rat hepatocytes. The same sequence was observed at each train of oscillations occurring between cells. The order of [Ca2+]i responses was modified neither by repeated additions of hormones nor by the hormonal dose. The mechanical disruption of an intermediate cell did not prevent the activation of the next cell. These results suggest that each hepatocyte in the multiplet displays its own sensitivity to the hormone and that a gradient of sensitivity between each cell could be responsible for directing the intercellular Ca2+ wave. To test this hypothesis, we selectively isolated rat hepatocytes from periportal (PP) and perivenous (PV) areas of the liver cell plate. Periportal (PP) and perivenous (PV) rat hepatocyte suspensions were loaded with quin2/AM and hormonal responses were studied in a spectrofluorimeter. Noradrenaline, angiotensin II, and vasopressin-induced [Ca2+]i rises were greater in PV than in PP hepatocytes. In contrast, PP cells were more responsive than PV cells to ATP. The function of the InsP3 receptor (InsP3R) was also studied by measuring the InsP3-mediated 45Ca2+ release from permeabilized PP and PV hepatocytes. In permeabilized PP and PV hepatocytes, internal Ca2+ stores displayed the same loading-kinetics, the responses to InsP3 were similar, and the sizes of InsP3-sensitive compartment were not different. In a further study, we investigated by video microscopy in fura2-loaded multicellular systems of rat hepatocytes, the mechanisms controlling intercellular propagation of the Ca2+ wave and coordination of Ca2+ signals induced by the different hormones. Using focal microperfusion which allows local perfusion of any cell of the multiplet, rapid agonist removal during the Ca2+ response and microinjection, we found that second messengers and [Ca2+]i rises in one hepatocyte cannot trigger Ca2+ responses in connected adjacent cells, suggesting that diffusion across gap junctions, while required for coordination, is not sufficient by itself for the propagation of the intercellular Ca2+ wave. In addition, focal microperfusion and intermediate cell dis

The present study demonstrates the susceptibility of astrocytes to infection with SIVmac251. Indeed, primary cultures of astrocytes derived from simian adult brains, can be infected in vitro with the SIVmac251. Results show that SIVmac251 establishes a persistent infection in primary astroglial cultures and that viral replication can be reactivated by TNF-alpha, GM-CSF, IFN-gamma. Viral proteins as Nef, Rev, Vpx and occasionally gp120/160 are evidenced by immunocytochemistry. In vivo SIVmac251 and/or HIV-2 infected astrocytes have been isolated from brains of macaques following ex vivo primary cultures. The whole of these results demonstrated that, in this model, SIV establishes a persistent state of infection of astrocytes, that viral replication can be reactivated by cytokines and moreover suggest strongly an in vivo infection of astrocytes in the brain of these infected macaques.

The tyrosine kinases of the Src family were first discovered due to their oncogenic properties. In untransformed fibroblasts, these kinases are activated as cells exists quiescence in response to some growth factors. Using microinjection to introduce catalytically inactive dominant-negative form of cSrc, as well as an antibody that neutralizes cSrc, Fyn and cYes, we have shown that Src kinases are required for DNA synthesis induced by most growth factors (PDGF, EGF, CSF-1, insulin, IGF-1). A functional link between Src kinases and the expression of the transcription factor c-Myc was also shown. In addition to cell growth promotion, some factors induce epithelial cell scattering and this also requires cSrc and cYes activities. However, in contrast to mitogenesis, they do not need novel gene expression for signalling but rather may act by phosphorylating components that regulate the cytoskeleton. Finally, increased Src kinase activities were found in several human carcinomas and we propose that these enzymes are involved in cell invasion.

Bacillus anthracis, a Gram positive bacterium, is the causative agent of anthrax. This organism is capsulogen and toxinogenic. It secretes two toxins which are composed of three proteins: the protective antigen (PA), the lethal factor (LF) and the edema factor (EF). The lethal toxin (PA + LF) provokes a subite death in animals, the edema toxin (PA + EF) induces edema. The edema and the lethal factors are internalised into the target cells via the protective antigen. EF and LF exert an adenylate cyclase and a metalloprotease activity respectively. The structure-function relationship of these three proteins were defined using in vitro and in vivo approaches.