Ceramide-induced formation of ROS and ATP depletion trigger necrosis in lymphoid cells

Villena J.; Henríquez M; Torres V.; Moraga, F; Diaz-Elizondo, J; Arredondo, C; Chiong M.; Olea Azar C.; Stutzin A.; Lavandero S.; Quest, AFG

Abstract

In lymphocytes, Fas activation leads to both apoptosis and necrosis, whereby the latter form of cell death is linked to delayed production of endogenous ceramide and is mimicked by exogenous administration of long- and short-chain ceramides. Here molecular events associated with noncanonical necrotic cell death downstream of ceramide were investigated in A20 B lymphoma and Jurkat T cells. Cell-permeable, C6-ceramide (C6), but not dihydro-C6-ceramide (DH-C6), induced necrosis in a time- and dose-dependent fashion. Rapid formation of reactive oxygen species (ROS) within 30 min of C6 addition detected by a dihydrorhodamine fluorescence assay, as well as by electron spin resonance, was accompanied by loss of mitochondrial membrane potential. The presence of N-acetylcysteine or ROS scavengers like Tiron, but not Trolox, attenuated ceramide-induced necrosis. Alternatively, adenovirus-mediated expression of catalase in A20 cells also attenuated cell necrosis but not apoptosis. Necrotic cell death observed following C6 exposure was associated with a pronounced decrease in ATP levels and Tiron significantly delayed ATP depletion in both A20 and Jurkat cells. Thus, apoptotic and necrotic death induced by ceramide in lymphocytes occurs via distinct mechanisms. Furthermore, ceramide-induced necrotic cell death is linked here to loss of mitochondrial membrane potential, production of ROS, and intracellular ATP depletion. © 2007 Elsevier Inc. All rights reserved.

Más información

Título según WOS: Ceramide-induced formation of ROS and ATP depletion trigger necrosis in lymphoid cells
Título según SCOPUS: Ceramide-induced formation of ROS and ATP depletion trigger necrosis in lymphoid cells
Título de la Revista: FREE RADICAL BIOLOGY AND MEDICINE
Volumen: 44
Número: 6
Editorial: Elsevier Science Inc.
Fecha de publicación: 2008
Página de inicio: 1146
Página final: 1160
Idioma: English
URL: http://linkinghub.elsevier.com/retrieve/pii/S0891584907008052
DOI:

10.1016/j.freeradbiomed.2007.12.017

Notas: ISI, SCOPUS