Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Although TRAIL (tumor necrosis factor (TNF)-related apoptosis inducing ligand) is a well-known apoptosis inducer, we have previously demonstrated that acidic extracellular pH (pHe) switches TRAIL-induced apoptosis to regulated necrosis (or necroptosis) in human HT29 colon and HepG2 liver cancer cells. Here, we investigated the role of RIPK1 (receptor interacting protein kinase 1), RIPK3 and PARP-1 (poly (ADP-ribose) polymerase-1) in TRAIL-induced necroptosis in vitro and in concanavalin A (Con A)-induced murine hepatitis. Pretreatment of HT29 or HepG2 with pharmacological inhibitors of RIPK1 or PARP-1 (Nec-1 or PJ-34, respectively), or transient transfection with siRNAs against RIPK1 or RIPK3, inhibited both TRAIL-induced necroptosis and PARP-1-dependent intracellular ATP depletion demonstrating that RIPK1 and RIPK3 were involved upstream of PARP-1 activation and ATP depletion. In the mouse model of Con A-induced hepatitis, where death of mouse hepatocytes is dependent on TRAIL and NKT (Natural Killer T) cells, PARP-1 activity was positively correlated with liver injury and hepatitis was prevented both by Nec-1 or PJ-34. These data provide new insights into TRAIL-induced necroptosis with PARP-1 being active effector downstream of RIPK1/RIPK3 initiators and suggest that pharmacological inhibitors of RIPKs and PARP-1 could be new treatment options for immune-mediated hepatitis.
ISSN: 1350-9047

inserm-00871432
http://www.hal.inserm.fr/inserm-00871432
DOI : 10.1038/cdd.2012.90
PUBMED : 22814620

Éditeur(s) : HAL CCSD Landes Bioscience
Résumé : International audience
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
Autophagy

hal-00735751
https://hal.archives-ouvertes.fr/hal-00735751
PUBMED : 22966490

Éditeur(s) : HAL CCSD European Geosciences Union (EGU)
Résumé : International audience
Holocene climate fluctuations and human activity since the Neolithic have shaped present-day Mediter-ranean environments. Separating anthropogenic effects from climatic impacts to better understand Mediterranean pale-oenvironmental changes over the last millennia remains a challenging issue. High-resolution pollen analyses were un-dertaken on two cores from the Palavasian lagoon system (Hérault, southern France). These records allow reconstruction of vegetation dynamics over the last 4500 years. Results are compared with climatic, historical and archeological archives. A long-term aridification trend is highlighted during the late Holocene, and three superimposed arid events are recorded at 4600–4300, 2800–2400 and 1300–1100 cal BP. These periods of high-frequency climate variability coincide in time with the rapid climatic events observed in the Atlantic Ocean (Bond et al., 2001). From the Bronze Age (4000 cal BP) to the end of the Iron Age (around 2000 cal BP), the spread of sclerophyllous taxa and loss of forest cover result from anthropogenic impact. Classical Antiquity is characterized by a major reforestation event related to the concentration of rural activity and populations in coastal plains leading to forest recovery in the mountains. A major regional deforestation occurred at the beginning of the High Middle Ages. Around 1000 cal BP, forest cover is minimal while the cover of olive, chestnut and walnut expands in relation to increasing human influence. The present-day vegetation dominated by Mediterranean shrubland and pines has been in existence since the beginning of the 20th century.
ISSN: 1814-9324

hal-01447627
https://hal-univ-tlse2.archives-ouvertes.fr/hal-01447627
https://hal-univ-tlse2.archives-ouvertes.fr/hal-01447627/document
https://hal-univ-tlse2.archives-ouvertes.fr/hal-01447627/file/Azuara%20et%20al%202015_cor.pdf
DOI : 10.5194/cp-11-1769-2015

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
An intensive water vapour intercomparison effort, involving airborne and ground-based water vapour lidar systems, was carried out in the framework of the COPS experiment. The main objective of this paper is to provide accurate error estimates for these systems. Comparisons between the ground-based Raman lidar BASIL and the airborne CNRS DIAL (Differential Absorption Lidar) indicate a mean relative bias between the two sensors, calculated with respect to the mean value of −2.13% (−0.034 g kg−1) in the altitude region 0.5-3.5 km, while comparisons between BASIL and the airborne DLR DIAL lead to a mean relative bias of 1.87% (0.018 g kg−1) in this same altitude region. Comparisons between the ground-based UHOH DIAL and the CNRS DIAL indicate a bias of −3.2% (−0.37 × 1022 m−3) in the altitude range 1.5-4.5 km, while comparisons between the UHOH DIAL and the DLR DIAL indicate a bias of 0.83% (0.06 × 1022 m−3) in this same altitude range. Based on the available comparisons between the ground-based Raman lidar BERTHA and the CNRS DIAL, the mean relative bias is found to be −4.37% (−0.123 g kg−1) in the altitude region 0.5-4.5 km. Comparisons between the ground-based IGN Raman lidar and the CNRS DIAL indicate a bias of 3.18% (0.55 g kg−1) in the altitude range from 0.5 to 4.5 km, while comparisons between the CNRS DIAL and DLR DIAL result in a mean relative bias of 3.93% (1.1 × 1022 m−3) in the altitude interval 0.5-4.0 km. Based on the available statistics of comparisons, benefiting from the fact that the CNRS DIAL was able to be compared with all other lidar systems, and putting equal weight on the data reliability of each instrument, overall relative values for BASIL, BERTHA, IGN Raman lidar, UHOH DIAL, DLR DIAL, and CNRS DIAL, with respect to the mean value, are found to be −0.38, −2.60, 4.90, −1.43, −2.23 and 1.72%, respectively.
ISSN: 0035-9009

hal-00572576
https://hal.archives-ouvertes.fr/hal-00572576
DOI : 10.1002/qj.697

Éditeur(s) : HAL CCSD
Résumé : TNF-Related Apoptosis-Inducing Ligand (TRAIL) is a well-known apoptosis inducer, which activates the extrinsic death pathway. TRAIL is pro-apoptotic on colon cancer cells, while not cytotoxic towards normal healthy cells. However, its clinical use is limited by cell resistance to cell death which occurs in approximately 50% of cancer cells. Short Chain Fatty Acids (SCFA) are also known to specifically induce apoptosis of cancer cells. In accordance, we have shown that food grade dairy propionibacteria induce intrinsic apoptosis of colon cancer cells, via the production and release of SCFA (propionate and acetate) acting on mitochondria. Here, we investigated possible synergistic effect between Propionibacterium freudenreichii and TRAIL. Indeed, we hypothesized that acting on both extrinsic and intrinsic death pathways may exert a synergistic pro-apoptotic effect. Whole transcriptomic analysis demonstrated that propionibacterial supernatant or propionibacterial metabolites (propionate and acetate), in combination with TRAIL, increased pro-apoptotic gene expression (TRAIL-R2/DR5) and decreased anti-apoptotic gene expression (FLIP, XIAP) in HT29 human colon cancer cells. The revealed synergistic pro-apoptotic effect, depending on both death receptors (TRAIL-R1/DR4, TRAIL-R2/DR5) and caspases (caspase-8, -9 and -3) activation, was lethal on cancer cells but not on normal human intestinal epithelial cells (HIEC), and was inhibited by Bcl-2 expression. Finally, milk fermented by P. freudenreichii induced HT29 cells apoptosis and enhanced TRAIL cytotoxic activity, as did P. freudenreichii DMEM culture supernatants or its SCFA metabolites. These results open new perspectives for food grade P. freudenreichii-containing products in order to potentiate TRAIL-based cancer therapy in colorectal cancer.
4 . International Symposium on Propionibacteria and Bibfidobacteria
Cork, Ireland

hal-01372131
https://hal.archives-ouvertes.fr/hal-01372131
PRODINRA : 371605

Éditeur(s) : HAL CCSD Wiley Open Access
Résumé : International audience
Estetrol (E4) is a natural estrogen with a long half-life produced only by the human fetal liver during pregnancy. The crystal structures of the estrogen receptor α (ERα) ligand-binding domain bound to 17β-estradiol (E2) and E4 are very similar, as well as their capacity to activate the two activation functions AF-1 and AF-2 and to recruit the coactivator SRC3. In vivo administration of high doses of E4 stimulated uterine gene expression, epithelial proliferation, and prevented atheroma, three recognized nuclear ERα actions. However, E4 failed to promote endothelial NO synthase activation and acceleration of endothelial healing, two processes clearly dependent on membrane-initiated steroid signaling (MISS). Furthermore, E4 antagonized E2 MISS-dependent effects in endothelium but also in MCF-7 breast cancer cell line. This profile of ERα activation by E4, uncoupling nuclear and membrane activation, characterizes E4 as a selective ER modulator which could have medical applications that should now be considered further.
ISSN: 1757-4676

hal-01118028
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118028
PUBMED : 25214462
PUBMEDCENTRAL : PMC4287935
DOI : 10.15252/emmm.201404112