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 Nature Publishing Group
Résumé : International audience
Collisional mountain belts grow as a consequence of continental plate convergence and eventuallydisappear under the combined effects of gravitational collapse and erosion. Using a decade ofGPS data, we show that the western Alps are currently characterized by zero horizontal velocityboundary conditions, offering the opportunity to investigate orogen evolution at the time ofcessation of plate convergence. We find no significant horizontal motion within the belt, but GPS andlevelling measurements independently show a regional pattern of uplift reaching ~2.5 mm/yr in thenorthwestern Alps. Unless a low viscosity crustal root under the northwestern Alps locally enhancesthe vertical response to surface unloading, the summed effects of isostatic responses to erosion andglaciation explain at most 60% of the observed uplift rates. Rock-uplift rates corrected from transientglacial isostatic adjustment contributions likely exceed erosion rates in the northwestern Alps. In theabsence of active convergence, the observed surface uplift must result from deep-seated processes.
ISSN: 2045-2322

hal-01357450
https://hal.archives-ouvertes.fr/hal-01357450
https://hal.archives-ouvertes.fr/hal-01357450/document
https://hal.archives-ouvertes.fr/hal-01357450/file/noquet2016.pdf
DOI : 10.1038/srep28404

Éditeur(s) : HAL CCSD Spandidos Publications
Résumé : International audience
ISSN: 1107-3756

hal-01122662
https://hal.archives-ouvertes.fr/hal-01122662

Éditeur(s) : HAL CCSD
Résumé : International audience
International Scientific Conference on Probiotics and Prebiotics (IPC)
Kosice, Slovakia

hal-01122606
https://hal.archives-ouvertes.fr/hal-01122606