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Mitochondrial cytochrome c release precedes transmembrane depolarisation and caspase-3 activation during ceramide-induced apoptosis of Jurkat T cells
journal contribution
posted on 2023-05-16, 13:34 authored by Hearps, AC, Burrows, J, Connor, CE, Gregory WoodsGregory Woods, Raymond Lowenthal, Scott RaggScott RaggWhilst 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 (Δψm) 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.
History
Publication title
ApoptosisVolume
7Issue
5Pagination
387-394ISSN
1360-8185Department/School
Tasmanian School of MedicinePublisher
Kluwer Academic PublPlace of publication
NetherlandRepository Status
- Restricted