Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection

Contact with HIV-1 envelope protein elicits release of ATP through pannexin-1 channels on target cells; by activating purinergic receptors and Pyk2 kinase in target cells, this extracellular ATP boosts HIV-1 infectivity

Sexual and reproductive health and human rights of women living with HIV

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138378/1/jia20834-sup-0001.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138378/2/jia20834.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138378/3/jia20834-sup-0002.pd

Etude des mécanismes régulant la mort cellulaire indépendante des caspases médiée par CD47 dans la leucémie lymphoïde chronique B (LLC-B)

Il arrive fréquemment que les lymphocytes B de Leucémie Lymphoïde Chronique B (LLC-B) présentent des anomalies qui les rendent résistantes à l apoptose classique induite par les traitements chimiothérapeutiques. Dans ce contexte, nos résultats montrent que la stimulation de CD47 induit une nouvelle voie de mort cellulaire qui reste fonctionnelle dans les cellules B de LLC-B, alors même qu elles se montrent résistantes à l apoptose classique. Cette mort est caractérisée exclusivement par des altérations cytoplasmiques et notamment mitochondriales. Celles-ci ne sont pas couplées à un relargage des protéines pro-apoptotiques et ne sont pas contrôlées par les protéines de la famille Bcl-2. En revanche, ces dysfonctionnements sont gouvernés par la translocation mitochondriale de la protéine Drp-1. Si les caspases ne sont pas impliquées dans ces processus, l ensemble des dommages cellulaires observés peuvent être inhibés par les inhibiteurs des serpases.PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

La mitochondrie au coeur du suicide cellulaire

La mort cellulaire programmée joue un rôle crucial dans le bon fonctionnement des organismes vivants et son dérèglement a été associé à de nombreux processus pathologiques. S'il a été identifié trois types de mort cellulaire programmée, toutes ont un effecteur commun : la mitochondrie. En effet, cet organelle initialement considéré comme n'étant que la source d'énergie de la cellule s'est révélé être une redoutable machine à tuer

Emergence of IFN-alpha TRAIL-expressing killer pDCs (IKpDCs) as a consequence of a crosstalk with NK cells. Influence of HIV-1 infection and implication of HMGB1

International audienceEmergence of IFN-alpha TRAIL-expressing killer pDCs (IKpDCs) as a consequence of a crosstalk with NK cells. Influence of HIV-1 infection and implication of HMGB

Identification and characterization of AIFsh2, a mitochondrial apoptosis-inducing factor (AIF) isoform with NADH oxidase activity.

Apoptosis-inducing factor (AIF) is a bifunctional NADH oxidase involved in mitochondrial respiration and caspase-independent apoptosis. Three alternatively spliced mRNA isoforms of AIF have been identified previously: AIF, AIF-exB, and AIFsh. Here, we report the cloning and the biochemical characterization of a new isoform named AIF short 2 (AIFsh2). AIFsh2 transcript includes a previously unknown exon placed between exons 9 and 10 of AIF. The resulting AIFsh2 protein, which localizes in mitochondria, corresponds to the oxidoreductase domain of AIF. In this way, AIFsh2 exhibits similar NADH oxidase activity to AIF and generates reactive oxygen species. Like AIF, AIFsh2 is released from mitochondria to cytosol after an apoptotic insult in a calpain or cathepsin-dependent manner. However, in contrast to AIF, AIFsh2 does not induce nuclear apoptosis. Thus, it seems that the reactive oxygen species produced by the oxidoreductase domain of AIF/AIFsh2 are not important for AIF-dependent nuclear apoptosis. In addition, we demonstrate that the AIFsh2 mRNA is absent in normal brain tissue, whereas it is expressed in neuroblastoma-derived cells, suggesting a different regulation in normal and transformed cells from the brain lineage. Together, our results reveal that AIF yields an original and independent genetic regulation of the two AIF functions. This is an important issue to understand the physiological role of this protein

AIFsh, a novel apoptosis-inducing factor (AIF) pro-apoptotic isoform with potential pathological relevance in human cancer.

International audienceAIF is a main mediator of caspase-independent cell death. It is encoded by a single gene located on chromosome X, region q25-26 and A6 in humans and mice, respectively. Previous studies established that AIF codes for two isoforms of the protein, AIF and AIF-exB. Here, we identify a third AIF isoform resulting from an alternate transcriptional start site located at intron 9 of AIF. The resulting mRNA encodes a cytosolic protein that corresponds to the C-terminal domain of AIF (amino acids 353-613). We named this new isoform AIFshort (AIFsh). AIFsh overexpression in HeLa cells results in nuclear translocation and caspase-independent cell death. Once in the nucleus, AIFsh provokes the same effects than AIF, namely chromatin condensation and large scale (50 kb) DNA fragmentation. In contrast, these apoptogenic effects are not precluded by the AIF-inhibiting protein Hsp70. These findings identify AIFsh as a new pro-apoptotic isoform of AIF, and also reveal that the first N-terminal 352 amino acids of AIF are not required for its apoptotic activity. In addition, we demonstrate that AIFsh is strongly down-regulated in tumor cells derived from kidney, vulva, skin, thyroid, and pancreas, whereas, gamma-irradiation treatment provokes AIFsh up-regulation. Overall, our results identify a novel member of the AIF-dependent pathway and shed new light on the role of caspase-independent cell death in tumor formation/suppression