Caspase-dependent initiation of apoptosis and necrosis by the Fas receptor in lymphoid cells: onset of necrosis is associated with delayed ceramide increase - PubMed (original) (raw)
. 2002 Dec 1;115(Pt 23):4671-83.
doi: 10.1242/jcs.00153.
Affiliations
- PMID: 12415011
- DOI: 10.1242/jcs.00153
Caspase-dependent initiation of apoptosis and necrosis by the Fas receptor in lymphoid cells: onset of necrosis is associated with delayed ceramide increase
Claudio A Hetz et al. J Cell Sci. 2002.
Expression of concern in
- Expression of Concern: Caspase-dependent initiation of apoptosis and necrosis by the Fas receptor in lymphoid cells: onset of necrosis is associated with delayed ceramide increase.
Hetz CA, Hunn M, Rojas P, Torres V, Leyton L, Quest AFG. Hetz CA, et al. J Cell Sci. 2022 Dec 1;135(23):jcs260736. doi: 10.1242/jcs.260736. Epub 2022 Dec 6. J Cell Sci. 2022. PMID: 36472158 No abstract available.
Abstract
Engagement of the Fas receptor promotes apoptosis by activation of caspases. In addition, alterations in plasma membrane lipid orientation and intracellular ceramide levels are often observed. In A20 B-lymphoma cells, FasL-induced cell death and phosphatidylserine (PS) externalization were completely prevented by the generic caspase inhibitor z-VAD-fmk. By contrast, the caspase-3 inhibitor Ac-DEVD-cho only partially restored cell viability and had no effect on surface exposure of PS. Flow cytometric analysis after FasL treatment identified two populations of dead cells. In one, death was dependent on caspase-3 and paralleled by DNA fragmentation and cell shrinkage. In the second, death occurred in the absence of caspase-3 activity and apoptotic features but was also blocked by zVAD-fmk. By morphological criteria these were identified as apoptotic and necrotic cells, respectively. Using fluorescent substrates, caspase-3 activity was detected only in the apoptotic cell population, whereas caspase-8 activity was detected in both. Both forms of caspase-8-dependent cell death were also detected downstream of Fas in Jurkat T-cells, where Fas-dependent PS externalization and delayed ceramide production, which is similar to results shown here in A20 cells, have been reported. However, for Raji B-cells, lacking lipid scrambling and ceramide production in response to Fas activation, only apoptosis was detected. Short-chain C2- or C6-ceramides, but not the respective inactive dihydro compounds or treatment with bacterial sphingomyelinase, induced predominantly necrotic rather than apoptotic cell death in A20 B-, Raji B- and Jurkat T-cells. Thus, delayed elevation of ceramide is proposed to promote necrosis in those Fas-stimulated cells where caspase-8 activation was insufficient to trigger caspase-3-dependent apoptosis.
Similar articles
- Ceramide-induced cell death is independent of the Fas/Fas ligand pathway and is prevented by Nur77 overexpression in A20 B cells.
Brás A, Albar JP, Leonardo E, de Buitrago GG, Martínez-A C. Brás A, et al. Cell Death Differ. 2000 Mar;7(3):262-71. doi: 10.1038/sj.cdd.4400653. Cell Death Differ. 2000. PMID: 10745271 - The tricyclodecan-9-yl-xanthogenate D609 triggers ceramide increase and enhances FasL-induced caspase-dependent and -independent cell death in T lymphocytes.
Milhas D, Andrieu-Abadie N, Levade T, Benoist H, Ségui B. Milhas D, et al. Int J Mol Sci. 2012;13(7):8834-8852. doi: 10.3390/ijms13078834. Epub 2012 Jul 16. Int J Mol Sci. 2012. PMID: 22942738 Free PMC article. - Ceramide-induced formation of ROS and ATP depletion trigger necrosis in lymphoid cells.
Villena J, Henriquez M, Torres V, Moraga F, Díaz-Elizondo J, Arredondo C, Chiong M, Olea-Azar C, Stutzin A, Lavandero S, Quest AF. Villena J, et al. Free Radic Biol Med. 2008 Mar 15;44(6):1146-60. doi: 10.1016/j.freeradbiomed.2007.12.017. Epub 2007 Dec 23. Free Radic Biol Med. 2008. PMID: 18191646 - Nitric oxide can inhibit apoptosis or switch it into necrosis.
Melino G, Catani MV, Corazzari M, Guerrieri P, Bernassola F. Melino G, et al. Cell Mol Life Sci. 2000 Apr;57(4):612-22. doi: 10.1007/PL00000723. Cell Mol Life Sci. 2000. PMID: 11130461 Free PMC article. Review. - How do necrotic cells expose phosphatidylserine to attract their predators-What's unique and what's in common with apoptotic cells.
Furuta Y, Zhou Z. Furuta Y, et al. Front Cell Dev Biol. 2023 Apr 5;11:1170551. doi: 10.3389/fcell.2023.1170551. eCollection 2023. Front Cell Dev Biol. 2023. PMID: 37091984 Free PMC article. Review.
Cited by
- The nutritional functions of dietary sphingomyelin and its applications in food.
Yang F, Chen G. Yang F, et al. Front Nutr. 2022 Oct 19;9:1002574. doi: 10.3389/fnut.2022.1002574. eCollection 2022. Front Nutr. 2022. PMID: 36337644 Free PMC article. Review. - Clinical significance of serum and follicular fluid ceramide levels in women with low ovarian reserve.
Timur B, Aldemir O, İnan N, Kaplanoğlu İ, Dilbaz S. Timur B, et al. Turk J Obstet Gynecol. 2022 Sep 23;19(3):207-214. doi: 10.4274/tjod.galenos.2022.05760. Turk J Obstet Gynecol. 2022. PMID: 36149261 Free PMC article. - Sphingolipids and Lymphomas: A Double-Edged Sword.
Pherez-Farah A, López-Sánchez RDC, Villela-Martínez LM, Ortiz-López R, Beltrán BE, Hernández-Hernández JA. Pherez-Farah A, et al. Cancers (Basel). 2022 Apr 19;14(9):2051. doi: 10.3390/cancers14092051. Cancers (Basel). 2022. PMID: 35565181 Free PMC article. Review. - Elephant Genomes Reveal Accelerated Evolution in Mechanisms Underlying Disease Defenses.
Tollis M, Ferris E, Campbell MS, Harris VK, Rupp SM, Harrison TM, Kiso WK, Schmitt DL, Garner MM, Aktipis CA, Maley CC, Boddy AM, Yandell M, Gregg C, Schiffman JD, Abegglen LM. Tollis M, et al. Mol Biol Evol. 2021 Aug 23;38(9):3606-3620. doi: 10.1093/molbev/msab127. Mol Biol Evol. 2021. PMID: 33944920 Free PMC article. - Podocyte Sphingolipid Signaling in Nephrotic Syndrome.
Li G, Kidd J, Gehr TWB, Li PL. Li G, et al. Cell Physiol Biochem. 2021 Apr 17;55(S4):13-34. doi: 10.33594/000000356. Cell Physiol Biochem. 2021. PMID: 33861526 Free PMC article. Review.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous