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 Oxford University Press (OUP)
Résumé : International audience
In this study we attempt to understand the water storage variations in a karst aquifer on the Larzac Plateau (South of France) using ground-based gravimetry. Surface to 60 m depth gravity measurements are performed three times a year since 2006 down a pothole, in complement to monthly absolute gravity (AG) measurements at three sites. The time variations of the surface to depth (STD) gravity differences are compared with the AG variations. Using a simple Bouguer plate model, we find that the STD gravity differences are very similar to the AG variations. The STD gravity differences are then used to determine apparent density values. These integrative density values are compared with measured grain densities from core samples to obtain an apparent porosity and saturation change representative of the investigated depth. The apparent porosity ranges from 4.8 to 7.3 per cent. We then discuss on the repartition of the apparent physical properties with respect to the epikarst and infiltration zone karst structures. We argue that AG and STD differences monitor epikarst water storage variations. Within this scope, we discuss the fact that seasonal scale water storage variation occurs predominantly in the epikarst.
ISSN: 0956-540X

hal-00413528
https://hal.archives-ouvertes.fr/hal-00413528
DOI : 10.1111/j.1365-246X.2009.04118.x