Claude Lefort et Cornelius Castoriadis : regards croisés sur Mai 68

Comme tous les moments révolutionnaires, Mai 68 n'est jamais complètement passé : il reste vivant pour la pensée politique contemporaine. En 1968, Cornelius Castoriadis et Claude Lefort, deux des principaux penseurs politiques de la France de l'après-guerre, proposaient leurs lectures des événements de Mai en France dans un livre important : Mai 68 : la Brèche. Pour le vingtième anniversaire des événements, ils écrivaient à nouveau sur ceux-ci, en cherchant à examiner leur postérité à la fois sociale et intellectuelle. Ces interprétations de Mai 68 font apparaître des convergences aussi bien que des oppositions théoriques entre les deux auteurs, qui concernent aussi bien le rôle de l'intellectuel que les définitions de la révolution, du pouvoir et de la démocratie. Mai 68 sert ainsi de révélateur, qui éclaire des aspects importants du dissensus politique et théorique qui a opposé Castoriadis à Lefort dès les années 1950.

Role of retroviral restriction factors in the interferon-α-mediated suppression of HIV-1 in vivo.

The antiviral potency of the cytokine IFN-α has been long appreciated but remains poorly understood. A number of studies have suggested that induction of the apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3 (APOBEC3) and bone marrow stromal cell antigen 2 (BST-2/tetherin/CD317) retroviral restriction factors underlies the IFN-α-mediated suppression of HIV-1 replication in vitro. We sought to characterize the as-yet-undefined relationship between IFN-α treatment, retroviral restriction factors, and HIV-1 in vivo. APOBEC3G, APOBEC3F, and BST-2 expression levels were measured in HIV/hepatitis C virus (HCV)-coinfected, antiretroviral therapy-naïve individuals before, during, and after pegylated IFN-α/ribavirin (IFN-α/riba) combination therapy. IFN-α/riba therapy decreased HIV-1 viral load by -0.921 (±0.858) log(10) copies/mL in HIV/HCV-coinfected patients. APOBEC3G/3F and BST-2 mRNA expression was significantly elevated during IFN-α/riba treatment in patient-derived CD4+ T cells (P < 0.04 and P < 0.008, paired Wilcoxon), and extent of BST-2 induction was correlated with reduction in HIV-1 viral load during treatment (P < 0.05, Pearson's r). APOBEC3 induction during treatment was correlated with degree of viral hypermutation (P < 0.03, Spearman's ρ), and evolution of the HIV-1 accessory protein viral protein U (Vpu) during IFN-α/riba treatment was suggestive of increased BST-2-mediated selection pressure. These data suggest that host restriction factors play a critical role in the antiretroviral capacity of IFN-α in vivo, and warrant investigation into therapeutic strategies that specifically enhance the expression of these intrinsic immune factors in HIV-1-infected individuals.

Epoxyeicosanoids stimulate multiorgan metastasis and tumor dormancy escape in mice.

Epoxyeicosatrienoic acids (EETs) are small molecules produced by cytochrome P450 epoxygenases. They are lipid mediators that act as autocrine or paracrine factors to regulate inflammation and vascular tone. As a result, drugs that raise EET levels are in clinical trials for the treatment of hypertension and many other diseases. However, despite their pleiotropic effects on cells, little is known about the role of these epoxyeicosanoids in cancer. Here, using genetic and pharmacological manipulation of endogenous EET levels, we demonstrate that EETs are critical for primary tumor growth and metastasis in a variety of mouse models of cancer. Remarkably, we found that EETs stimulated extensive multiorgan metastasis and escape from tumor dormancy in several tumor models. This systemic metastasis was not caused by excessive primary tumor growth but depended on endothelium-derived EETs at the site of metastasis. Administration of synthetic EETs recapitulated these results, while EET antagonists suppressed tumor growth and metastasis, demonstrating in vivo that pharmacological modulation of EETs can affect cancer growth. Furthermore, inhibitors of soluble epoxide hydrolase (sEH), the enzyme that metabolizes EETs, elevated endogenous EET levels and promoted primary tumor growth and metastasis. Thus, our data indicate a central role for EETs in tumorigenesis, offering a mechanistic link between lipid signaling and cancer and emphasizing the critical importance of considering possible effects of EET-modulating drugs on cancer.

FXYD Proteins Reverse Inhibition of the Na+-K+ Pump Mediated by Glutathionylation of Its {beta}1 Subunit.

The seven members of the FXYD protein family associate with the Na(+)-K(+) pump and modulate its activity. We investigated whether conserved cysteines in FXYD proteins are susceptible to glutathionylation and whether such reactivity affects Na(+)-K(+) pump function in cardiac myocytes and Xenopus oocytes. Glutathionylation was detected by immunoblotting streptavidin precipitate from biotin-GSH loaded cells or by a GSH antibody. Incubation of myocytes with recombinant FXYD proteins resulted in competitive displacement of native FXYD1. Myocyte and Xenopus oocyte pump currents were measured with whole-cell and two-electrode voltage clamp techniques, respectively. Native FXYD1 in myocytes and FXYD1 expressed in oocytes were susceptible to glutathionylation. Mutagenesis identified the specific cysteine in the cytoplasmic terminal that was reactive. Its reactivity was dependent on flanking basic amino acids. We have reported that Na(+)-K(+) pump β(1) subunit glutathionylation induced by oxidative signals causes pump inhibition in a previous study. In the present study, we found that β(1) subunit glutathionylation and pump inhibition could be reversed by exposing myocytes to exogenous wild-type FXYD3. A cysteine-free FXYD3 derivative had no effect. Similar results were obtained with wild-type and mutant FXYD proteins expressed in oocytes. Glutathionylation of the β(1) subunit was increased in myocardium from FXYD1(-/-) mice. In conclusion, there is a dependence of Na(+)-K(+) pump regulation on reactivity of two specifically identified cysteines on separate components of the multimeric Na(+)-K(+) pump complex. By facilitating deglutathionylation of the β(1) subunit, FXYD proteins reverse oxidative inhibition of the Na(+)-K(+) pump and play a dynamic role in its regulation.

La question de la politique dans la pensée du politique de Claude Lefort

La contribution propose une exploration longitudinale de la manière dont s'articulent chez Lefort, d'une part, sa compréhension des dimensions constitutives du politique avec, d'autre part, sa lecture d'événements singuliers de la politique française. La période considérée va de Mai 68 aux événements de l'hiver 1995. On montre que le cadre théorique d'arrière-plan, ce que Lefort appelle "le politique", commande très largement la lecture qu'il fait des événements par lesquels il se laisse convoquer. Plus précisément, on montre que, conçu sous l'interpellation de l'expérience totalitaire, ce cadre s'ordonne pour penser les choses politiques à la lumière de la différence totalitarisme/démocratie. Et du même coup, n'est pas en mesure d'accorder un caractère politiquement signifiant à ce qui se déroule dans la "sphère économique", en particulier le fantastique creusement des inégalités survenu depuis au moins la moitié des années 80 du siècle dernier. S'il est vrai que le totalitarisme, sous son visage "soviétique" en tout cas, semble ne plus constituer une menace politique crédible, on s'interroge, pour conclure, sur la pertinence de l'approche lefortienne dans la perspective des luttes émancipatrices.