39 research outputs found
Cellular Function of TRIM E3 Ubiquitin Ligases in Health and Disease
No full text: The field of the Tripartite Motif (TRIM) family has progressively attracted increasing interest during the last two decades [...]
Solange Desagher and Jean-Claude Martinou: Executioners of Cell Death
No full textInternational audienc
Trim17, novel E3 ubiquitin-ligase, initiates neuronal apoptosis
No full textAccumulating data indicate that the ubiquitin-proteasome system controls apoptosis by regulating the level and the function of key regulatory proteins. In this study, we identified Trim17, a member of the TRIM/RBCC protein family, as one of the critical E3 ubiquitin ligases involved in the control of neuronal apoptosis upstream of mitochondria. We show that expression of Trim17 is increased both at the mRNA and protein level in several in vitro models of transcription-dependent neuronal apoptosis. Expression of Trim17 is controlled by the PI3K/Akt/GSK3 pathway in cerebellar granule neurons (CGN). Moreover, the Trim17 protein is expressed in vivo, in apoptotic neurons that naturally die during post-natal cerebellar development. Overexpression of active Trim17 in primary CGN was sufficient to induce the intrinsic pathway of apoptosis in survival conditions. This pro-apoptotic effect was abolished in Bax(-/-) neurons and depended on the E3 activity of Trim17 conferred by its RING domain. Furthermore, knock-down of endogenous Trim17 and overexpression of dominant-negative mutants of Trim17 blocked trophic factor withdrawal-induced apoptosis both in CGN and in sympathetic neurons. Collectively, our data are the first to assign a cellular function to Trim17 by showing that its E3 activity is both necessary and sufficient for the initiation of neuronal apoptosis. Cell Death and Differentiation (2010) 17, 1928-1941; doi: 10.1038/cdd.2010.73; published online 18 June 201
NF-Y is essential for expression of the proapoptotic bim gene in sympathetic neurons
No full textNeuronal apoptosis has a major role during development and aberrant apoptosis contributes to the pathology of certain neurological conditions. Studies with nerve growth factor (NGF)-dependent sympathetic neurons have provided important insights into the molecular mechanisms of neuronal apoptosis and the signalling pathways that regulate the cell death programme in neurons. The BH3-only protein Bim is a critical mediator of apoptosis in many cell types and in sympathetic neurons is required for NGF withdrawal-induced death. However, regulation of bim expression is complex and remains incompletely understood. We report that a conserved inverted CCAAT box (ICB) in the rat bim promoter is bound by the heterotrimeric transcription factor NF-Y. Interestingly, NF-Y is required for bim promoter activity and its induction following NGF withdrawal. We demonstrate that NF-Y activity is essential for endogenous Bim expression and contributes to NGF withdrawal-induced death. Furthermore, we find that the transcriptional coactivators CBP and p300 interact with NF-Y and FOXO3a and bind to this region of the bim promoter. The amount of CBP/p300 bound to bim increases after NGF deprivation and inhibition of CBP/p300 activity reduces bim induction. Our results indicate that NF-Y cooperates with FOXO3a to recruit CBP/p300 to the bim promoter to form a stable multi-protein/DNA complex that activates bim transcription after survival factor withdrawal
Prévision, Détermination Analytique et Optimisation du Pouvoir Méthanogène de Boues Résiduaires Biologiques Variées
No full textAstrocytes protect neurons from hydrogen peroxide toxicity
No full textRecent reports indicate that neurons are particularly sensitive to hydrogen peroxide (H2O2). The present study was undertaken to investigate the putative role of astrocytes in the modulation of the neurotoxic effect of H2O2. The exposure to H2O2 of cultured striatal neurons from mouse embryos induced a concentration-dependent (10–1000 microM) cell death as estimated 24 hr later. Two methods were used to estimate neuronal survival: the 3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide assay or an enzyme-linked immunosorbent assay with antibodies directed against an antigen located in neurons (microtubule-associated protein-2). The neurotoxic effect of H2O2 on neurons cocultured with astrocytes was strongly attenuated compared with that observed on a pure population of neurons seeded at the same density. Moreover, the protective effect of astrocytes depended on the astrocytes/neurons ratio, a significant neuroprotection being detectable for 1 astrocyte to 20 neurons. Catalase seems to be the main hydrogen peroxidase activity involved in the neuroprotective effect of astrocytes. Indeed, in the culture conditions used, this enzymatic activity was enriched in this cell type compared with neurons; its inhibition, and not that of glutathione peroxidase, reduced the disappearance rate of the oxidant. On the contrary, glutathione peroxidase appeared to be the main enzymatic activity involved in the neuronal defense against H2O2 toxicity. Therefore, astrocytes could delay neuronal death in pathological situations in which H2O2 has been, at least partially, demonstrated to be involved.</jats:p
Predicting Amine Mist Formation Based on Aerosol Number Concentration and Size Measurements in Flue Gas
No full textAbstractAmine based solvent used for CO2 capture can be lost during the process due to: degradation, vaporization, mechanical losses and aerosol (mist) formation. Only recently, studies have appeared pointing out that aerosols can dominate the total amine emission at pilot plant scale behind coal fired power plants. Future full scale amine scrubber installations will be imposed emission limit values (ELV) for a number of components including NH3 and the amine itself. Most likely these ELV will be expressed as maximum concentrations tolerated in the CO2 poor flue gas leaving the stack so it is important to prevent or cure amine aerosol emission. The study presents a novel combination of two existing measurement techniques, that measure: (i) amine emissions from the top of the absorber using FTIR and (ii) PSD of the incoming flue gas using the ELPI+. The study is the first to show how combining these two measurement techniques allows to predict the presence or absence of mist formation. This hypothesis is based on information obtained during several measurement campaigns on different pilot plants
Thermodynamic analysis of the populations of charge carriers in dissociable binary semiconductors
No full textPost-translational modification of Bid has differential effects on its susceptibility to cleavage by caspase 8 or caspase 3
No full textBid is instrumental in death receptor-mediated apoptosis where it is cleaved by caspase 8 at aspartate 60 and aspartate 75 to generate truncated Bid (tBID) forms that facilitate release of mitochondrial cytochrome c. Bid is also cleaved at these sites by caspase 3 that is activated downstream of cytochrome c release after diverse apoptotic stimuli. In this context, tBid may amplify the apoptotic process. Bid is phosphorylated in vitro by casein kinases that regulate its cleavage by caspase 8 (Desagher, S., Osen-Sand, A., Montessuit, S., Magnenat, E., Vilbois, F., Hochmann, A., Journot, L. Antonsson, A., and Martinou, J.-C. (2001) Mol. Cell 8, 601-611). Using a Bid decapeptide substrate, we observed that phosphorylation at threonine 59 inhibited cleavage by caspase 8. This was also seen when recombinant Bid (rBid) and Bid isolated from murine kidney were incubated with casein kinase 11. However, there were differences in the susceptibility of rBid and isolated Bid to cleavage by caspases 3 and 8. Caspase 8 cleaved rBid to generate two C-terminal products, p15 and p13 tBid, but produced only p15 tBid from isolated Bid. Contrary to rBid, isolated Bid was resistant to cleavage by caspase 3, yet was readily cleaved within the cytosolic milieu. Our data suggest that one or more distinct cellular mechanisms regulate Bid cleavage by caspases 8 and 3 in situ
