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Mitochondrial cytochrome c release precedes transmembrane depolarisation and caspase-3 activation during ceramide-induced apoptosis of Jurkat T cells

Citation

Hearps, AC and Burrows, J and Connor, CE and Woods, GM and Lowenthal, RM and Ragg, SJ, Mitochondrial cytochrome c release precedes transmembrane depolarisation and caspase-3 activation during ceramide-induced apoptosis of Jurkat T cells, Apoptosis, 7, (5) pp. 387-394. ISSN 1360-8185 (2002) [Refereed Article]

DOI: doi:10.1023/A:1020034906200

Abstract

Whilst the role of ceramide, a second messenger of the sphingolipid family, in the initiation of receptor-mediated apoptosis is controversial, a growing body of evidence is emerging for a role of ceramide in the amplification of apoptosis via mitochondrial perturbations that culminate in the activation of execution caspases. Treatment of Jurkat T cells with the cell-permeable analog, C 2-ceramide, resulted in the rapid onset of apoptosis as evidenced by Annexin V-FITC staining of externalised phosphatidylserine residues. Cells bearing this early apoptotic marker had a reduced mitochondrial transmembrane potential ("ψm) that was preceded by the release of cytochrome c from mitochondria. Subsequent activation of caspase-3 provides the link between these ceramide-induced mitochondrial changes and execution caspases that ultimately result in the physical destruction of the cell. Collectively these results demonstrate that ceramide signalling results in caspase-mediated apoptosis via mitochondrial cytochrome c release and are further supportive of the role of ceramide in the amplification of apoptosis.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Clinical Sciences
Research Field:Clinical Sciences not elsewhere classified
Objective Division:Health
Objective Group:Other Health
Objective Field:Health not elsewhere classified
Author:Hearps, AC (Ms Anna Hearps)
Author:Burrows, J (Ms Joanna Burrows)
Author:Connor, CE (Mr Charles Connor)
Author:Woods, GM (Professor Gregory Woods)
Author:Lowenthal, RM (Professor Ray Lowenthal)
Author:Ragg, SJ (Dr Scott Ragg)
ID Code:24388
Year Published:2002
Web of Science® Times Cited:34
Deposited By:Medicine (Discipline)
Deposited On:2002-08-01
Last Modified:2003-03-20
Downloads:0

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