Fiche publication
Date publication
janvier 2006
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MARTINY Laurent
,
Pr MORJANI Hamid
,
Pr DEVARENNE-CHARPENTIER Emmanuelle
,
Pr ANTONICELLI Franck
,
Dr SCHNEIDER Christophe
,
Dr EL BTAOURI Hassan
Tous les auteurs :
El Btaouri H, Rath G, Morjani H, Schneider C, Petitfrere E, Antonicelli F, Martiny L
Lien Pubmed
Résumé
The programmed cell death plays a crucial role in the regulation of numerous physiological and pathological phenomena. In this study, we show that interleukin-1 beta (IL-1beta) induces an early production of endogenous ceramides via N-sphingomyelinase (N-Smase) as well as an inhibition of adenylyl cyclase activity in pig thyroid cells. This effect is followed by a down-regulation of the extracellular signal-regulated protein kinase (ERK1/2) phosphorylation, an activation of caspase-3, and ends by setting up the programmed cell death. The permeable exogenous C(2)-ceramide reproduces IL-1beta effects on: (i) inhibition of adenylyl cyclase activity, (ii) down-regulation of ERK1/2 phosphorylation, (iii) activation of caspase-3, and (iv) apoptosis in pig thyroid cells. Cell treatment with a PKA inhibitor down-regulates ERK1/2 phosphorylation. Furthermore, inhibition of ERK1/2 signaling pathway by U-0126 enhances caspase-3 activity and sets up programmed cell death. Both IL-1beta and exogenous C(2)-ceramide effects are reproduced by U-0126 so illustrating the implication of ERK1/2 down-regulation in both caspase-3 activation and apoptosis induction. Our study shows for the first time that endogenous ceramides are important second messengers in IL-1beta-induced apoptosis in pig thyroid cells through inhibition of adenylyl cyclase and ERK1/2 activities.
Référence
Biochem Biophys Res Commun. 2006 Jan 13;339(2):469-76
