Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/60648
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | Induction of apoptosis in human mitogen-activated peripheral blood T-lymphocytes by the ether phospholipid ET-18-OCH3: Involvement of the Fas receptor/ligand system |
Autor: | Cabaner, Christelle; Gajate, Consuelo CSIC ORCID ; Mollinedo, Faustino CSIC ORCID | Fecha de publicación: | 1999 | Editor: | Wiley-Blackwell | Citación: | British Journal of Pharmacology 127(4): 813-825 (1999) | Resumen: | Activated T-cells constitute a target for treatment of autoimmune diseases. We have found that the antitumour ether phospholipid 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3; edelfosine) induced dose- and time-dependent apoptosis in human mitogen-activated peripheral blood T-lymphocytes, but not in resting T-cells. T-lymphocytes were stimulated with phytohemagglutinin and interleukin-2 or with concanavalin A. Apoptosis was assessed by DNA fragmentation through cell cycle and TUNEL analyses, as well as through visualization of internucleosomal DNA fragmentation in agarose gels. The ET-18-OCH3-mediated apoptotic response in activated T-lymphocytes was less intense than in human leukaemic T cell lines, such as Jurkat cells and Peer cells; namely about 25% apoptosis in activated T-cells versus about 46–61% apoptosis in T leukaemic cells after 24 h treatment with 10 μM ET-18-OCH3. The ET-18-OCH3 thioether analogue BM 41.440 (ilmofosine) showed a similar apoptotic capacity to that found with ET-18-OCH3 in activated T-cells, whereas the phospholipid analogue hexadecylphosphocholine (miltefosine) failed to promote this response. The uptake of [3H]-ET-18-OCH3 was much larger in activated T-cells than in resting lymphocytes. Using a cytofluorimetric approach we have found that ET-18-OCH3 induced disruption of the mitochondrial transmembrane potential and production of reactive oxygen species in activated T-cells, but not in resting lymphocytes. ET-18-OCH3 induced an increase in Fas (APO-1/CD95) ligand mRNA expression in activated T-cells, and incubation with a blocking anti-Fas (APO-1/CD95) antibody partially inhibited the ET-18-OCH3-induced apoptosis of activated T-lymphocytes. These results demonstrate that mitogen-activated T-cells, unlike resting lymphocytes, are able to take up significant amounts of ET-18-OCH3, and are susceptible to undergo apoptosis by the ether lipid via, in part, the Fas (APO-1/CD95) receptor/ligand system. This ET-18-OCH3 apoptotic action can be of importance in the therapeutic action of this ether lipid in certain autoimmune diseases. | URI: | http://hdl.handle.net/10261/60648 | DOI: | 10.1038/sj.bjp.0702606 | Identificadores: | doi: 10.1038/sj.bjp.0702606 issn: 0007-1188 e-issn: 1476-5381 |
Aparece en las colecciones: | (IBMCC) Artículos (IBGM) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
accesoRestringido.pdf | 15,38 kB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
PubMed Central
Citations
12
checked on 21-abr-2024
SCOPUSTM
Citations
52
checked on 23-abr-2024
WEB OF SCIENCETM
Citations
50
checked on 22-feb-2024
Page view(s)
332
checked on 21-abr-2024
Download(s)
101
checked on 21-abr-2024
Google ScholarTM
Check
Altmetric
Altmetric
Artículos relacionados:
NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.